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Image Source:Koch Institute

LIVE – OCTOBER 17 – DAY 2- Koch Institute Immune Engineering Symposium 2017, MIT, Kresge Auditorium

Koch Institute Immune Engineering Symposium 2017

Image Source: Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Aviva Lev-Ari, PhD, RN will be in attendance covering the event in REAL TIME





  • The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The Immune System and Therapeutics (Series D: BioMedicine & Immunology) Kindle Edition – on since September 4, 2017



8:30 – 9:45 Session V
Moderator: Stefani Spranger | MIT, Koch Institute

K. Christopher Garcia – Stanford University
Exploiting T Cell and Cytokine Receptor Structure and Mechanism to Develop New Immunotherapeutic Strategies

  • T Cell Receptor, peptide-MHC, 10 to the power of 10 is combinatorics – Library for selection to determine enrichment possibilities
  • Ligand identification for orphan TCRs
  1. Industrializing process
  2. use pMHC
  • IL-2 – Receptor Signaling Complex
  • Effector cells (NK, T)
  • Engineered  T Cell – Tunable expansion, ligand-Receptor interface
  • Randomize IL-2RBeta interface: Orthogonal receptor vs wild type
  • In Vivo adoptive transfer model: to quantify orthogonality ratio
  • CD4, CD8, Treg,C57BL/6J
  • Ligand discovery
  • Orthogonal IL-2

Stefani Spranger – MIT, Koch Institute
Batf3-DC as Mediators of the T Cell-Inflamed Tumor Microenvironment

  • Melanoma – solid cancer and other types, Immune inhibitory regulatory pathway patient with Immune response present
  • T cell-inflamed Tumor vs Non-T cell-inflamed Tumor
  • identify oncogenic pathways differentially activated between T cell-inflamed and non-Tcell-inflamed infiltration
  • If on Tumor:
  1. Braf/PTEN
  2. Braf/CAT
  3. Braf/PTEN/CAT
  • The role of T cell priming – lack of initial
  • Beta-catenin-expressing tumors fail to prime 2C TCR-transgenic T cells
  • Deficiency in number of CD8+ and CD103+ dendritic cells
  • CD103+ DC are essential for T cell Priming and T cell-inflammation #StefaniSpranger
  • Adoptive transfer of effector 2C T cells fails to control Beta-catenin+ tumors
  • Vaccination induced anti-gen specific T cell memory fails to control Beta-catenin+ tumors
  • What cell type in tumor microenvironment effect monilization of T cell
  • CD103+ Dendritic cellsare source chymokine
  • Recruitment of effector T cells: Reconstitution od Beta-catenin-expressing SIY+
  • Are Batf3-DC within the tumor required for the recruitment of effector T cells?
  • Tumor-residing Batf3-drive CD103+ DC are required for the recruitment of effector T cells
  • Gene spore for correlation with recturment of effector cells
  • T cell Priming – CD103+ DC are essential for effector T cells

George Georgiou – University of Texas at Austin
The Human Circulating Antibody Repertoire in Infection, Vaccination or Cancer

  • Serological Antibody Repertoire: in blood or in secretions
  • Antibody in serum – is difficult sequence identity
  • Serum IgG – 7-17 mg/ml if less immune deficient if more hyper globular
  • antibodies produced in long lived plasma cells in the bone marrow — experimentally inaccessible
  • Discovery of antibodies from the serological repertoire – not B cells
  • BM-PCs
  • Serum antibodies function via Fc effector mechanism – complement activation
  • Ig-SEQ – BCR-SEQ
  • Repertoire-wide computational modelling of antibody structures
  • En masse analysis & Mining of the Human Native Antibody Repertoire
  • hypervariable – High-Throughput Single B Cell VH:VL (or TCRalpha, beta) sequencing
  • EBOV Vaccinee Peak ASCs (day 8) mining: Neutralization
  • Features of the Serum Antibody Repertoire to Vaccine ANtigens:The Serum IgG Repertoire is Highly Polarized
  • Each bar represents a distinct antibody lineage
  • Serum IgG Repertoire becomes increasingly polarized with AGE >50 – may be predictive of tumor development process
  • Human Norovirus – explosive Diarreha, chromically infected – HuNoV BNAb Discovery – Takeda 214 bivalent Vaccine – Binding antibodies binding to avccine antigen VLP
  • HuNoV causes 800 death in the US per year of immune deficient
  • Influenza Trivalent Vaccine: Antibodies to hemaggiutinin: H1, H3, and B COmponenet
  • Abundant H1 +H3 Serum IgGs do not neutralize but confer Protection toInfluenza challenge with Live Virus #GeorgeGeorgiou
  • Non-Neutralizing Antibodies: The role of Complement in Protection

9:45 – 10:15 Break

10:15 – 11:30 Session VI
Moderator: K. Dane Wittrup | MIT, Koch Institute

Harvey Lodish – Whitehead Institute and Koch Institute
Engineered Erythrocytes Covalently Linked to Antigenic Peptides Can Protect Against Autoimmune Disease

  • Modified Red blood cells are microparticles for introducing therapeutics & diagnostics into the human body
  • Bool transfusion is widely used therapeutics
  • Covalently linking unique functional modalities to mouse or human red cells produced in cell culture:
  • PRODUCTION OF HUMAN RED BLOD CELLS EXPRESSING A FOREIN PROTEIN: CD34+ stem/progenitor cells that generates normal enucleated RBC.
  • PPAR-alpha and glucocorticoticoid receptor
  • Norman morphology: Sortase A is a bactrial transpeptidase that covalently links a “donor”
  • Engineering Normal Human RBC biotin-LPETG
  • Covelantely – Glycophorin A with camelid VHHs specific for Botulinum toxin A or B
  • Generation of immuno tolerance: SOruggable Mature RBCs: CRISPR mice expressing Kell-LPETG
  • Ovalbumin as Model Antigens:
  1. OBI B,
  2. OTI CD8 T cells
  3. OTII CD4 T cells
  4. OT-1
  5. OT-2
  • RBC induced peptides challenged and experiences apoptosis
  • Type I Diabetes in NOD mice
  • RBCs bearing InsB9-23 – prevented development of diabetes

Multiple sclerosis

  • MOG – Myelin Oligodend

Sai Reddy – ETH Zurich
Molecular Convergence Patterns in Antibody Responses Predict Antigen Exposure

  • Clonal diversity – estimating the size of antibody repertoire: 10 to power of 18 or 10 to 13
  • Clonal selection in antibody repertoire
  • Convergent selection in antibody repertoire
  • Convergent selection in TCR repertoire complex have restriction with MCH interactions
  • How molecular abundance of convergence predicts antigen exposure identify antigen-associated clusters #SaiReddy
  • molecular convergence 0 gene expression analysis, immunization scheme molecular bar coding to correct errors
  • Recoding antibody repertoire sequence space: Cross correlation reveals different clusters
  • Building a classifier model based on cluster frequency: Clones from immunized mice
  • epitope specificity is driving antibody repertoire response
  • deep learning,

K. Dane Wittrup – MIT, Koch Institute
Temporal Programming of Synergistic Innate and Adaptive Immunotherapy

  • Innate effector functions of anti-tumor antibodies
  • Innate & adaptive Immunotherapy
  • Innate mAb –>> tumor cell; adaptive CD8+ T cells
  • Chemokines Antigens
  • Cytokines Chemokines – back and forth innate Adaptive –> <— neutrophils impact
  • AIPV vaccine:
  • How anti-TAA mAbs helping T cell Immune response
  • Anti-TAA mAbs drive vaccinal T cell responses: NK cells
  • antibody drives T cells responses: alpha-TAA mAbs potentiate T cell therapies: ACT +MSA-IL-2 vs alphaPD-1 + vaccine
  • CD8+ T cells required for alpha TAA mAb efficacy- In absence of T cells Treatment does not work
  • Anti-TAA mAb +Fc/IL-2 induces intramural cytokine storm #KDaneWittrup
  • How to simplify and improve AIPV? Hypothesis: ALign dose schedule
  • Immune response to infection follwos a temporal progression: Innate … Adaptive
  • Antigenic material kill cells: Chemo, cell death Antigen presentation, T cell priming, T cell recirculation, Lymphocyte tumor infiltrate, TCR
  • IFN alpha 2 dys after mAb +Il-2: Curative: days post tumor injection
  • Necessary components: CD8+ T cells & DC, Macrophages,
  • Optimal IFNalpha coincides with max innate response vs Mature DCs after antigen loading #KDaneWittrup
  • Optimal timing od agent administration effect on Therapy Outcome: IL-2, IFNalpha, TAAmAb
  • Cytkine timing can be better than protein engineering #KDaneWittrup

11:30 – 1:00 Lunch Break

1:00 – 2:15 Session VII
Moderator: Michael Birnbaum | MIT, Koch Institute

Kai Wucherpfennig – Dana-Farber Cancer Institute
Discovery of Novel Targets for Cancer Immunotherapy

  • POSITIVE STRESS SIGNAL during malignant Transformation
  • NKG2G=D Receptor: MICA/B Results in Immune escape – Proteolytic cleavage  shedding of MICA/B present in serum, indication of tumor progression
  • Shed MICA vs Surface MICA/B – restore NK cell cytotoxicity and IFNgamma Production
  • Human NK cells express NKG2D and Fc Receptors
  • Synergistic NKG2D and CD16 signaling enhances NK cell cytootxicity: Control IgG vs Anti NKG2D
  • MICA Antibody induces Immunity Against Lung Metastases
  • NK cells are required to inhibit Growth of metastases: Anti-CD8beta,
  • Contribution to Therapeutic Efficacy: NKG2D and CD16 Receptors #KaiWucherpfennig
  • Strategy to analyze Pulmonary NK cells: Activation and expression
  • Single cell RNA-seq of lung NK cells Revealed higher infiltration of activated NK cells: Isotype vs 7C6-migG2a
  • Cytokines and Chemokines produce NK cells
  • MICA/B increaces NK
  •  Induction of Tumor cell Apoptosis
  • Xenotransplant Model with Human Melanoma Cel Line A2058
  • Lung metastasis, liver metastasis
  • Inhibition of human melanoma Metastases in NSG Mice Reconstitute with Human NK
  • Liver metastases are controlled by Myeloid Cells that include Kupffer cells

Michael Birnbaum – MIT, Koch Institute
An Unbiased Determination of pMHC Repertoires for Better Antigen Prediction

  • Vaccines TCR gene therapy adoptive T cel therapy
  • Tumor genone – Tumor pMHC repertoire = Tumor TCR repertoire T cell repertoire
  • Neoantigen vaccines as a personalized anti-cancer therapy
  • Tumor procurement – Target selection – personal vaccine production – vaccine administration
  • Prediction of neoantigen-MHC Binding due to polimorphism affecting recognition, rare in MHC Allells #Michael Birnbaum
  • Antigenicity – Chaperones HLA-DM sculp the peptide binding repertoire of MHC
  • Identification of loaded peptide ligands: pMHC mass spectroscopy of tissue
  • TCR recognition, pMHC yeast display: Cleave peptide-MHC linker, catalyze peptide exchange
  • HLA-DR4 library design and selection to enrich HLA-DM: Amino Acid vs Peptide position: Depleted vs Enriched – relative to expected for NNK codon
  •  6852 _ predicted to bind vs 220 Non-binding peptides
  • HLA polymorphism: repertoire differences caused by
  • Antigen – T cell-driven antigen discovery: engaging Innate and Adaptive Immune response
  • Sorting TIL and select: FOcus of T cell-driven antigen discovery
  • T cell-driven antigen discovery: TCR

Jennifer R. Cochran – Stanford University
Innate and Adaptive Integrin-targeted Combination Immunotherapy

  • alpa-TAA
  • Targeting Integrin = universal target involved in binding to several receptors: brest, lung, pancreatic, brain tumors arising by mutations – used as a handle for binding to agents
  • NOD201 Peptide-Fc Fusion: A Psudo Ab
  • Handle the therapeutics: NOD201 + alphaPD1
  • NOD201 effectively combines with alphaPD-L1, alphaCTLA-4, and alpha4-1BB/CD137
  • Corresponding monotherapies vs ComboTherapy invoking Innate and Adaptive Immune System
  • Microphages, CD8+ are critical vs CD4+ Neutrophils, NK cells, B cells #JenniferR. Cochran
  • Macrophages activation is critical – Day 4, 4 and 5
  • NOD201 + alphaPD1 combo increases M1 macrophages
  • Who are the best responders to PD1 – genes that are differentially expressed
  • NOD201 deives T cells reaponses through a “vaccinal” effect
  • CAncer Immune CYcle
  • Integrin – localization
  • Prelim NOD201 toxicity studies: no significant effects
  • Targeting multiple integrins vs antibodies RJ9 – minimal effect
  • NOD201 – manufacturability – NEW AGENT in Preclinical stage

2:15 – 2:45 Break

2:45 – 3:35 Session VIII
Moderator: Jianzhu Chen | MIT, Koch Institute

Jennifer Wargo – MD Anderson Cancer Center
Understanding Responses to Cancer Therapy: The Tissue is the Issue, but the Scoop is in the Poop

  • Optimize Targeted Treatment response
  • Translational research in patients on targeted therapy revealed molecular and immune mechanisms of response and resistance
  • Molecular mechanisms – T cell infiltrate after one week of therapy
  • Role of tumor stroma in mediating resistance to targeted therapy
  • Tumor microenvironment
  • Intra-tumoral bacteria identified in patients with Pancreatic Cancer
  • Translational research in patients on immune checkpoint blockade revealed molecualr and immune mechanism of response and resistance
  • Biomarkers not found
  • SYstemic Immunity and environment (temperature) on response to checkpoint blockade – what is the role?
  • Role of mIcrobiome in shaping response to checkpoint blockade in Melanoma
  • Microbime and GI Cancer
  • Diversity of the gut microbiome is associated with differential outcomes in the setting of stem cell transplant in AML
  • Oral and gut fecal microbiome in large cohort patient with metastatic melanoma undergoing systemic therapy
  • Repeat oral & gut AFTER chemo
  • WGSeq – Diversity of microbiome and response (responders vs non-responders to anti PD-1 – High diversity of microbiome have prolonged survival to PD-1 blockade
  • Anti tumor Immunity and composition of gut microbiome in patient on anti-PD-1 favorable AND higher survival #JenniferWargo
  • Enhance therapeutic responses in lang and renal carcinoma: If on antibiotic – poorer survival
  • sharing data important across institutions

Jianzhu Chen – MIT, Koch Institute
Modulating Macrophages in Cancer Immunotherapy

  • Humanized mouth vs de novo human cancer
  • B cell hyperplasia
  • double hit lymphoma
  • AML
  • Overexpression of Bcl-2 & Myc in B cells leads to double-hit lymphoma
  • antiCD52 – CLL
  • Spleen, Bone marrow, Brain
  • Microphages are required to kill Ab-bound lymphoma cells in vivo #JianzhuChen
  • COmbinatorial chemo-Immunotherapy works for solid tumors: treating breast cancer in humanized mice
  • Infiltration of monocytic cells in the bone marrow
  • Cyclophosphophamide-antibody synergy extending to solid tumor and different antibodies #JianzhuChen
  • Polarization of macrophages it is dosage-dependent M1 and M2
  • Antibiotic induces expression of M1 polarizing supresses development and function of tumor-associated macrophages (TAM)
  • Antibiotic inhibits melanoma growth by activating macrophages in vivo #JianzhuChen



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Image Source:Koch Institute


LIVE – OCTOBER 16 – DAY 1- Koch Institute Immune Engineering Symposium 2017, MIT, Kresge Auditorium

Koch Institute Immune Engineering Symposium 2017




Image Source: Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Aviva Lev-Ari, PhD, RN will be in attendance covering the event in REAL TIME





  • The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The Immune System and Therapeutics (Series D: BioMedicine & Immunology) Kindle Edition – on since September 4, 2017



7:00 – 8:15 Registration

8:15 – 8:30Introductory Remarks
Darrell Irvine | MIT, Koch Institute; HHMI

  • Stimulating the Immune system not only sustaining it for therapies

K. Dane Wittrup | MIT, Koch Institute

8:30 – 9:45Session I
Moderator: Douglas Lauffenburger | MIT, Biological Engineering and Koch Institute

Garry P. Nolan – Stanford University School of Medicine
Pathology from the Molecular Scale on Up

  • Intracellular molecules,
  • how molecules are organized to create tissue
  • Meaning from data Heterogeneity is an illusion: Order in Data ?? Cancer is heterogeneous, Cells in suspension – number of molecules
  • System-wide changes during Immune Response (IR)
  • Untreated, Ineffective therapy, effective therapy
  • Days 3-8 Tumor, Lymph node…
  • Variation is a Feature – not a bug: Effective therapy vs Ineffective – intercellular modules – virtual neighborhoods
  • ordered by connectivity: very high – CD4 T-cells, CD8 T-cels, moderate, not connected
  • Landmark nodes, Increase in responders
  • CODEX: Multiples epitome detection
  • Adaptable to proteins & mRNA
  • Rendering antibody staining via removal to neighborhood mapping
  • Human tonsil – 42 parameters: CD7, CD45, CD86,
  • Automated Annotations of tissues: F, P, V,
  • Normal BALBs
  • Marker expression defined by the niche: B220 vs CD79
  • Marker expression defines the niche
  • Learn neighborhoods and Trees
  • Improving Tissue Classification and staining – Ce3D – Tissue and Immune Cells in 3D
  • Molecular level cancer imaging
  • Proteomic Profiles: multi slice combine
  • Theory is formed to explain 3D nuclear images of cells – Composite Ion Image, DNA replication
  • Replication loci visualization on DNA backbone – nascent transcriptome – bar code of isotopes – 3D  600 slices
  • use CRISPR Cas9 for Epigenetics

Susan Napier Thomas – Georgia Institute of Technology
Transport Barriers in the Tumor Microenvironment: Drug Carrier Design for Therapeutic Delivery to Sentinel Lymph Nodes

  • Lymph Nodes important therapeutics target tissue
  • Lymphatic flow support passive and active antigen transport to lymph nodes
  • clearance of biomolecules and drug formulations: Interstitial transport barriers influence clearance: Arteriole to Venule –
  • Molecular tracers to analyze in vivo clearance mechanisms and vascular transport function
  • quantifying molecular clearance and biodistribution
  • Lymphatic transport increases tracer concentrations within dLN by orders of magnitude
  • Melanoma growth results in remodeled tumor vasculature
  • passive transport via lymphatic to dLN sustained in advanced tumors despite abrogated cell trafficking
  • Engineered biomaterial drug carriers to enhance sentinel lymph node-drug delivery: facilitated by exploiting lymphatic transport
  • TLR9 ligand therapeutic tumor in situ vaccination – Lymphatic-draining CpG-NP enhanced
  • Sturcutral and Cellular barriers: transport of particles is restriced by
  • Current drug delivery technology: lymph-node are undrugable
  • Multistage delivery platform to overcome barriers to lymphatic uptake and LN targeting
  • nano particles – OND – Oxanorbornade OND Time sensitive Linker synthesized large cargo – NP improve payload
  • OND release rate from nanoparticles changes retention in lymph nodes – Axilliary-Brachial delivery
  • Two-stage OND-NP delivery and release system dramatically – OND acumulate in lymphocyte
  •  delivers payload to previously undraggable lymphe tissue
  • improved drug bioactivity  – OND-NP eliminate LN LYMPHOMAS
  • Engineered Biomaterials

Douglas Lauffenburger – MIT, Biological Engineering and Koch Institute
Integrative Multi-Omic Analysis of Tissue Microenvironment in Inflammatory Pathophysiology

  • How to intervene, in predictive manner, in immunesystem-associated complex diseases
  • Understand cell communication beteen immune cells and other cells, i.e., tumor cells
  • Multi-Variate in Vivo – System Approach: Integrative Experiment & COmputational Analysis
  • Cell COmmunication & Signaling in CHronic inflammation – T-cell transfer model for colitis
  • COmparison of diffrential Regulation (Tcell transfer-elicited vs control) anong data types – relying solely on mRNA can be misleading
  • Diparities in differential responses to T cell transfer across data types yield insights concerning broader multi-organ interactions
  • T cell transfer can be ascertained and validated by successful experimental test
  • Cell COmmunication in Tumor MIcro-Environment — integration of single-cell transcriptomic data and protein interaction
  • Standard Cluster Elucidation – Classification of cell population on Full gene expression Profiles using Training sets: Decision Tree for Cell Classification
  • Wuantification of Pairwise Cell-Cell Receptor/Ligand Interactions: Cell type Pairs vs Receptor/Ligand Interaction
  • Pairwise Cell-Cell Receptor/Ligand Interactions
  • Calculate strength of interaction and its statistical significance
  • How the interaction is related to Phenotypic Behaviors – tumor growth rate, MDSC levels,
  • Correlated the Interactions translated to Phynotypic behavior for Therapeutic interventions (AXL via macrophage and fibroblasts)
  • Mouth model translation to Humans – New machine learning approach
  • Pathways, false negative, tumor negative expression
  • Molecular vs Phynotypical expression
  • Categories of inter-species translation
  • Semi-supervised Learning ALgorithms on Transcriptomic Data can ascertain Key Pathways/Processes in Human IBD from mapping mouse IBD

9:45 – 10:15 Break

10:15 – 11:30Session II
Moderator: Tyler Jacks | MIT, Koch Institute; HHMI

Tyler Jacks – MIT, Koch Institute; HHMI
Using Genetically Engineered Mouse Models to Probe Cancer-Immune Interactions

  • Utility of genetically-engineered mouse models of Cancer:
  1. Immune Response (IR),
  2. Tumor0immune microenvironment
  • Lung adenocarcinoma – KRAS mutation: Genetically-engineered model, applications: CRISPR, genetic interactions
  • Minimal Immune response to KP lung tumors: H&E, T cells (CD3), Bcells (B220) for Lenti-x 8 weeks
  • Exosome sequencing : Modeling loss-and gain-of-function mutations in Lung Cancer by CRISPR-Cas9 – germline – tolerance in mice, In vivo CRISPR-induced knockout of Msh2
  • Signatures of MMR deficient
  • Mutation burden and response to Immunotherapy (IT)
  • Programmed neoantigen expression – robust infiltration of T cells (evidence of IR)
  • Immunosuppression – T cell rendered ineffective
  • Lymphoid infiltration: Acute Treg depletion results in T cell infiltration — this depletion causes autoimmune response
  • Lung Treg from KP tumor-bearing mice have a distinct transcriptional heterogeneity through single cell mRNA sequencing
  • KP, FOXP3+, CD4
  • Treg from no existent to existance, Treg cells increase 20 fold =>>>  Treg activation and effectiveness
  • Single cells cluster by tissue and cell type: Treg, CD4+, CD8+, Tetramer-CD4+
  • ILrl1/II-33r unregulated in Treg at late time point
  • Treg-specific deletion of IL-33r results in fewer effector Tregs in Tumor-bearing lungs
  • CD8+ T cell infiltration
  • Tetramer-positive T cells cluster according to time point: All Lung CD8+ T cells
  • IR is not uniform functional differences – Clones show distinct transcriptional profiles
  • Different phynotypes Exhaustive signature
  • CRISPR-mediated modulation of CD8 T cell regulatory genes
  • Genetic dissection of the tumor-immune microenvironment
  • Single cell analysis, CRISPR – CRISPRa,i, – Drug development

Wendell Lim – University of California, San Francisco

Synthetic Immunology: Hacking Immune Cells

  • Precision Cell therapies – engineered by synthetic biology
  • Anti CD19 – drug approved
  • CAR-T cells still face major problems
  1. success limited to B cells cancers = blood vs solid tumors
  2. adverse effects
  3. OFF-TUMOR effects
  • Cell engineering for Cancer Therapy: User remote control (drug) – user control safety
  • Cell Engineering for TX
  1. new sensors – decision making for
  2. tumor recognition – safety,
  3. Cancer is a recognition issue
  • How do we avoid cross-reaction with bystader tissue (OFF TISSUE effect)
  • Tumor recognition: More receptors & integration
  • User Control
  • synthetic NOTCH receptors (different flavors of synNotch) – New Universal platform for cell-to -cell recognition: Target molecule: Extracellular antigen –>> transciptional instruction to cell
  • nextgen T cell: Engineer T cell recognition circuit that integrates multiple inputs: Two receptors – two antigen priming circuit
  • UNARMED: If antigen A THEN receptor A activates CAR
  • “Bystander” cell single antigen vs “tumor” drug antigen
  • Selective clearance of combinatorial tumor – Boulian formulation, canonical response
  • Cell response: Priming –>> Killing: Spatial & Temporal choreographed cell
  • CAR expression while removed from primed cells deminished
  • Solid Tumor: suppress cell microenvironment: Selected response vs non-natural response
  • Immune stimulator IR IL2, IL12, flagellin in the payload — Ourcome: Immune enhancement “vaccination”
  • Immune suppression –  block
  • Envision ideal situation: Unarmed cells
  • FUTURE: identify disease signatures and vulnerabilities – Precision Medicine using Synthetic Biology

Darrell Irvine – MIT, Koch Institute; HHMI
Engineering Enhanced Cancer Vaccines to Drive Combination Immunotherapies

  • Vaccine to drive IT
  • Intervening in the cancer-immunity cycle – Peptide Vaccines
  • poor physiology  of solute transport to tissue
  • endogenous albumin affinity – Lymphe Node dying
  • Designing Albumin-hitchhiking vaccines
  • Amphiphile-vaccine enhance uptake in lymph nodes in small and large animal models
  • soluble vaccine vs Amphiphile-vaccine
  • DIRECTING Vaccines to the Lymph nodes
  • amph-peptide antigen: Prime, booster, tetramer
  • albimin-mediated LN-targeting of both antigen and adjuvant maximizes IR
  • Immuno-supressed microenvironment will not be overcome by vaccines
  • Replacing adoptive T cell transfer with potent vaccine
  • exploiting albumin biology for mucosal vaccine delivery by amph-vaccines
  • Amph-peptides and -adjuvants show enhanced uptake/retention in lung tissue
  •  Enhancing adoptive T cell therapy: loss of T cell functionality, expand in vivo
  • boost in vivo enhanced adoptive T cell therapy
  • CAR-T cells: Enable T cells to target any cell surface protein
  • “Adaptor”-targeting CAR-T cells to deal with tumor cell heterogeneity
  • Lymph node-targeting Amph as CAR T booster vaccine: prining, production of cytokines
  • Boosting CAR T with amph-caccines: anti FITC CAR-T by DSPE=PEG-FITC coated
  • Targeting FITC to lymph node antigen presenting cells
  • Modulatory Macrophages
  • Amph-FITC expands FITC-CAR T cells in vivo – Adjuvant is needed
  • Hijacking albumin’s natural trafficking pathway

11:30 – 1:00  Lunch Break

1:00 – 2:15Session III
Moderator: Darrell Irvine | MIT, Koch Institute; HHMI

Nicholas P. Restifo – National Cancer Institute
Extracellular Potassium Regulates Epigenetics and Efficacy of Anti-Tumor T Cells

Why T cell do not kill Cancer cells?

  • co-inhibition
  • hostile tumor microenvironment

CAR T – does not treat solid tumors

Somatic mutation

  1. resistence of T cell based IT due to loss of function mutations
  2. Can other genes be lost?

CRISPR Cas9 – used to identify agents – GeCKOv2 Human library

Two cell-type (2CT) CRISPR assay system for genome-wide mutagenesis

  • work flow for genome-scale SRISPR mutagenesis profiling of genes essential for T cell mediate cytosis
  • sgRNA enrichment at the individual gene level by multiple methods:
  1. subunits of the MHC Class I complex
  2. CRISPR mutagenesis cut germline
  • Measutring the generalizability of resistance mechanism and mice in vivo validation
  • Validation of top gene candidates using libraries: MART-1
  • Checkpoint blockade: cells LOF causes tumor growth and immune escape
  • Weird genesL Large Ribisomal Subunit Proteins are nor all essential for cell survival
  • Bias in enrichment of 60S vs 40S
  • Novel elements of MHC class I antigen processing and presentation
  • Association of top CRISPR hits with response rates to IT – antiCTLA-4
  • CRISPR help identify novel regulators of T cells
  • Analyzed sgRNA – second rarest sgRNA for gene BIRC2 – encoded the Baculoviral Inhibitor
  • Drugs that inhibit BIRC2
  • How T cells can kill tumor cells more efficiently
  • p38kiaseas target for adoptive immunotherapy
  • FACS-based – Mapk14
  • Potent targets p38 – Blockade PD-1 or p38 ??
  • p38 signaling: Inhibition augments expansion and memory-marked human PBMC and TIL cells, N. P. Restifo
  • Tumor killing capacity of human CD19-specific, gene engineered T cells

Jennifer Elisseeff – Johns Hopkins University
The Adaptive Immune Response to Biomaterials and Tissue Repair

  • design scafolds, tissue-specific microenvironment
  • clinical translation of biosynthetic implants for soft tissue reconstruction
  • Local environment affects biomaterials: Epidermis, dermis
  • CD4+ T cells
  • Immune system – first reponders to materials: Natural or Synthetic
  • Biological (ECM) scaffolds to repair muscle injury
  • Which immune cells enter the WOUND?
  • ECM alters Macrophages: CD86, CD206
  • Adaptive system impact on Macrophages: CD86
  • mTOR signaling pathway M2 depend on Th2 Cells in regeneration of cell healing of surgical wounds
  • Systemic Immunological changes
  • Is the response antigen specific? – IL-4 expression in ILN,
  • Tissue reconstruction Clinical Trial: FDA ask to look at what cells infiltrate the scaffold
  • Trauma/biomaterial response – Injury induction of Senescence, anti apoptosis
  • Injury to skin or muscle
  • Is pro-regenerative environment (Th2/M2) pro-tumorigenic?
  • SYNTHETIC Materials for scafolds
  • Biomaterials and Immunology
  1. Immune response to bioscafolds
  2. environment modulate the immune system
  • Regenerative Immunetherapy

Marcela Maus – Massachusetts General Hospital

Engineering Better T Cells

  • Comparing CD19 CARs for Leukemia – anti-CD19- directed CAR T cells with r/r B-cell ALL – age 3-25 – FDA approved Novartis tisagenlecleucel – for pediatric r/r/ ALL
  • Phase II in diffuse large B cell lymphoma. Using T cells – increases prospects for cure
  • Vector retroviral – 30 day expression
  • measuring cytokines release syndrome: Common toxicity with CAR 19
  • neurological toxicity, B-cell aplagia
  • CART issues with heme malignancies
  1. decrease cytokine release
  2. avoid neurological toxicity – homing
  3. new targets address antigene escape variants – Resistance, CD19 is shaded, another target needed
  4. B Cell Maturation Antigen (BCMA) Target
  5. Bluebird Bio: Response duratio up to 54 weeks – Active dose cohort
  6. natural ligand CAR based on April
  7. activated in response to TACI+ target cells – APRIL-based CARs but not BCMA-CAR is able to kill TACI+ target cells
  • Hurdles for Solid Tumors
  1. Specific antigen targets
  2. tumor heterogeneity
  3. inhibitory microenvironment
  • CART in Glioblastoma
  1. rationale for EGFRvIII as therapeutic target
  2. Preclinical Studies & Phase 1: CAR t engraft, not as highly as CD19
  3. Upregulation of immunosuppression and Treg infiltrate in CART EGFRvIII as therapeutic target, Marcela Maus
  • What to do differently?


2:15 – 2:45 Break

2:45 – 4:00 Session IV
Moderator: Arup K. Chakraborty | MIT, IMES

Laura Walker – Adimab, LLC
Molecular Dissection of the Human Antibody Response to Respiratory Syncytial Virus

  • prophylactic antibody is available
  • Barriers for development of Vaccine
  • Prefusion and Postfusion RSV structures
  • Six major antigenic sites on RSV F
  • Blood samples Infants less 6 month of age and over 6 month: High abundance RSV F -specific memory B Cells are group  less 6 month

Arup K. Chakraborty – MIT, Institute for Medical Engineering & Science
How to Hit HIV Where it Hurts

  • antibody  – Model IN SILICO
  • Check affinity of each Ab for the Seaman panel of strain
  • Breadth of coverage
  • immmunize with cocktail of variant antigens
  • Mutations on Affinity Maturation: Molecular dynamics
  • bnAb eveolution: Hypothesis – mutations evolution make the antigen binding region more flexible,
  • Tested hypothesisi: carrying out affinity maturation – LOW GERMLINE AFFINITY TO CONSERVE RESIDUES IN 10,000 trials, acquire the mutation (generation 300)

William Schief – The Scripps Research Institute
HIV Vaccine Design Targeting the Human Naive B Cell Repertoire

  • HIV Envelope Trimer Glycan): the Target of neutralizing Antibodies (bnAbs)
  • Proof of principle for germline-targeting: VRC)!-class bnAbs
  • design of a nanoparticle
  • can germline -targeting innumogens prime low frequency precursors?
  • Day 14 day 42 vaccinate
  • Precursor frequency and affinity are limiting for germline center (GC) entry at day 8
  • Germline-targeting immunogens can elicit robust, high quality SHM under physiological conditions of precursor frequency and affinity at day 8, 16, 36
  • Germline-targeting immunogens can lead to production of memory B cells

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17th Annual EmTech @ Media Lab, MIT – November 7 – 8, 2017, Cambridge, MA – This Year’s Themes, Speakers and Agenda

MIT Media Lab
Building E14
75 Amherst Street 
(Corner of Ames and Amherst)


  • Business Impact
  • Connectivity
  • Intelligent Machines
  • Rewriting Life
  • Sustainable Energy
  • Meet the Innovators Under 35

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston


will cover in REAL TIME

The 17th annual EmTech MIT – A Place of Inspiration, November 7 – 8, 2017, Cambridge, MA

In attendance, streaming LIVE using Social Media

Aviva Lev-Ari, PhD, RN






  • 8:00
    Registration & Breakfast
  • 9:00
    Opening Remarks
  • 9:15
    The State of AI
  • 9:45
    Meet the Innovators Under 35
  • 10:30
    Break & Networking
  • 11:00
    AI’s Next Leap Forward
  • 12:30
    Lunch & Networking
  • 2:00
    Adapting to the reality of climate change
  • 3:30
    Break & Networking
  • 4:00
    Meet the Innovators Under 35
  • 5:30
    Lemelson-MIT Prize Honors & Reception


  • 8:00
    Registration & Breakfast
  • 9:00
    What is social media doing to society?
  • 10:30
    Break & Networking
  • 11:00
    Next-generation brain interfaces
  • 12:00
    Lunch & Networking
  • 1:30
    The Future of Work
  • 2:00
    A Look Ahead: Emerging Technologies at Work
  • 3:00
    Break & Networking
  • 3:30
    Meet the Innovators Under 35
  • 5:00
    2017 Innovator Under 35 Awards & Reception


  • Viktor

    Group Leader, Broad Institute of MIT and Harvard

    2017 Innovator Under 35

  • Gene

    CEO, Sila Nano

    2017 Innovator Under 35

  • Tracy

    Founding Advisor, Project Include

    2017 Innovator Under 35

  • Adrienne

    Software Engineer, Google

    2017 Innovator Under 35

  • Phillipa

    Assistant Professor, University of Massachusetts, Amherst

    2017 Innovator Under 35

  • Tallis

    CEO, Singu

    2017 Innovator Under 35

  • Kathy

    CEO, WafaGames

    2017 Innovator Under 35

  • Ian

    Staff Research Scientist, Google Brain

    2017 Innovator Under 35

  • Yasmin

    Director of Research and Development, Jigsaw at Google

    Addressing Online Threats to Global Security

  • Kris

    Chief Scientist and Cofounder, Narrative Science

    AI’s Language Problem

  • Svenja

    Scientist, Fraunhofer IGB

    2017 Innovator Under 35

  • Reid

    Cofounder, LinkedIn; Partner, Greylock Partners

    The Future of Work

  • John

    Professor, Harvard University

    Climate Disruption: Technical Approaches to Mitigation and Adaptation

  • Joi

    Director, MIT Media Lab

    The Future of Work

  • Mary Lou

    Founder, Openwater

    Capturing Our Imagination: The Evolution of Brain-Machine Interfaces

  • David

    Professor, Harvard University; Founder, Carbon Engineering

    The Growing Case for Geoengineering

  • Neha

    Cofounder and CTO, Confluent

    2017 Innovator Under 35

  • Andrew

    Founder,; Adjunct Professor, Stanford University

    The State of AI

  • Tomaso

    Investigator, McGovern Institute; Eugene McDermott Professor, Brain and Cognitive Sciences, MIT

    Understanding Intelligence

  • Olga

    Assistant Professor, Princeton University

    2017 Innovator Under 35

  • Michael

    Marie Curie Fellow, EPFL

    2017 Innovator Under 35

  • Gang

    Chief Scientist, Alibaba

    2017 Innovator Under 35

  • Jianxiong

    Chief Executive Officer, AutoX, Inc.

    2017 Innovator Under 35

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Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

Top, from left: James Allison and Lieping Chen. Bottom, from left: Gordon Freeman, Tasuku Honjo (NOT ATTENDED), Arlene Sharpe.

Aviva Lev-Ari, PhD, RN was in attendance and covered this event LIVE


The 2017 Warren Alpert Foundation Prize has been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancer’s ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

  • James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center – Immune checkpoint blockage in Cancer Therapystrictly Genomics based drug
  1. 2017 FDA approved a gemonics based drug
  2. and co-stimulatory signals
  3. CTLA-4 blockade, CD28, AntiCTLA-4 induceses regression of Transplantable Murine tumo
  4. enhance tumor-specific immune response
  5. Fully antibody human immune response in 10,000 patients – FDA approved 2011
  6. Metastatic melanoma – 3 years survival, programmed tumor death, PD-1, MHC-A1
  7. Ipi/Nivo vs. Ipi – combination – 60% survival vs Ipi alone
  8. Anti CTA4 va Anti-PD-1
  9. responsive T cell population – MC38 TILs
  10. MC38 Infiltrating T cell populations: Treg, CD4, Effector, CD8, NKT/gamma-delta
  11. Checkpoint blockage modulates infiltrating T cell population frequencies
  12. T reg correlated with Tumor growth
  13. Combination therapy lead to CURE survival at 80% rate vs CTAL-4 40% positive outcome

Not Attended — Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University – Immune regulation of Cancer Therapy by PD-1 Blockade


  • Lieping Chen, United Technologies Corporation Professor in Cancer Research and Professor of immunobiology, of dermatology and of medicine, Yale University – Adoptive Resistance: Molecular Pathway t Cancer Therapy – focus on solid tumors
  1. Enhancement – Enhance normal immune system – Co-stimulation/Co-inhibition Treg, and Cytokines, adoptive cell therapy, Lymphoid organs stores
  2. Normalization – to correct defective immune system – normalizing tumor immunity, diverse tumor escape mechanisms
  3. Anti-PD therapy: regression of large solid tumors: normalizing tumor immunity targeting tumor microenvironment: Heterogeneity, functional modulation, cellular and molecular components – classification by LACK of inflamation, adaptive resistance, other inhibitory pathways, intrinsic induction
  4. avoid autoimmune toxicity,
  5. Resetting immune response (melanoma)
  6. Understad Resistance: Target missing resistance or Adaptive resistance Type II= acquired immunity
  • Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School – PD-L1/PD-1 Cancer Immunotherapy
  1. B7 antibody
  2. block pathway – checkpoint blockage, Expand the T cells after recognition of the disease. T cell receptor signal, activation, co -stimulatory: B71 molecule, B72 – survival signals and cytokine production,.Increased T cell proliferation,
  3. PDL-1 is a ligand of PD 1. How T cell die? genes – PD1 Gene was highly expressed,
  4. Interferon gamma upregulate PD-L1 expression
  5. Feedback loop Tumor – stimulating immune response, interferon turn off PD1
  6. PD-L1 and PD-L2 Expression: Interferom
  7. Trancefuctor MHC, B7-2
  8. PD-L! sisgnat inhibit T-cell activation: turn off Proliferation and cytokine production — Decreasing the immune response
  9. T cell DNA Content: No S-phase devided cell
  10. PD-L1 engagement of PD-1 results in activation : Pd-1 Pathway inhibits T Cell Actiivation – lyposite motility,
  11. Pd-L2 is a second ligand for PD-1 and inhibits T cell activation
  12. PDl-1 expression: BR CA, Ovarian, Colonol-rectal, tymus, endothelial
  13. Blockage of the Pathway – Immune response enhanced
  14. Dendritic cells express PD-L1, PD-L2 and combination of Two, Combination was best of all by increase of cytokine production, increasing the immune response.
  15. PD-L1 blockade enhanced the immune response , increase killing and increased production of cytokines,
  16. anti-tumor efficacy of anti-PD-1/Pd-L1
  17. Pancreatic and colono-rector — PD-L, PDL1, PDL2 — does not owrkd.
  18. In menaloma: PD-1 works better than CYLA-4
  19. Comparison of Targeted Therapy: BRAF TKI vs Chemo high % but short term
  20. Immunotherapy – applies several mechanism: pre-existing anti-therapy
  21. Immune desert: PD=L does not work for them
  23. PD blockage + nutrients and probiotic
  24. Tumor Genome Therapy
  25. Tumore Immuno-evasion Score
  26. Antigens for immune response – choose the ones
  27. 20PD-1 or PD-L1 drugs in development


  • Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women’s Hospital – Multi-faceted Functionsof the PD-1 Pathway
  1. function of the pathway: control T cell activation and function of maintain immune tolerance
  2. protect tissues from damage by immune response
  3. T cell dysfunction during cancer anf viral infection
  4. protection from autoimmunity, inflammation,
  5. Mechanism by which PD-1 pathway inhibits anti-tumor immunity
  6. regulation of memoryT cell responce of PD-1
  7. PD-1 signaling inhibit anti-tumor immunity
  8. Compare: Mice lacking CD8-Cre- (0/5) cleared vs PD-1-/-5/5 – PD-1 DELETION: PARTIAL AND TIMED: DELETION OF PD-1 ON HALF OG TILS STARTING AT DAY 7 POSTTUMOR IMPLANTATION OF BOTH PD-1 AND PD-1 TILS: – Tamoxifen days 7-11
  9. Transcription profile: analysis of CD8+ TILs reveal altered metabolism: Fatty Acid Metabolism vs Oxidative Phosphorylation
  10. DOes metabolic shift: WIld type mouth vs PD-1-/_ P14: analyze Tumor cell killingPD-1-/- enhanced FAO increases CD8+ T cell tocicity
  11. Summary: T cell memory development and PD-1: T effectors vs T cell memory: Primary vs Secondary infection: In the absent of PD-1, CD8+ T cels show increase expansion of T cells
  12. INFLUENZA INFECTION: PRIMARY more virus in lung in PD-1 is lacking
  13. Acute infection: PD-1 controls memory T cell differentiation vs PD-1 increase expansion during effector phase BUT impaired persistence during memory phase: impaired cytokine production post re-challenge
  14. PD-1 immunotherapy work for patients with tumor: Recall Response and Primary response
  15. TIL density Primary vs Long term survivor – 5 days post tumor implantation – rechallenged long term survival
  16. Hot tumor vs Cold tumor – Deletion of PD-1 impairs T memory cell development


Opening Remarks: George Q. Daley, MD, PhD, DEAN, HMS

  • Scientific collaboration check point – avoid the body attacking itself, sabotaging the immune system
  • 1987 – Vaccine for HepB
  • Eight of the awardees got the Nobel Prize


Moderated by Joan Brugge, PhD, HMS, Prof. of Cell Biology

  • Evolution of concepts of Immunotherapy: William Coley’s Toxin streptoccocus skin infection.
  • 20th century: Immuno-surveilence, Immune response – field was dead in 1978 replaced by Immunotherapy
  • Rosenberg at NIH, high dose of costimulatory molecule prevented tumor reappearanceantbody induce tumor immunity–>> immune theraphy by check point receptor blockade – incidence of tumor in immune compromised mice – transfer T cell
  • T cell defficient, not completely defficient, self recognition of tumor,
  • suppress immmune – immune evasion
  • Michael Atkins, MD, Detupy Director, Georgetown-Lombardi, Comprehensive Cancer Center Clinical applications of Checkpoint inhibitors: Progress and Promise
  1. Overwhelm the Immune system, hide, subvert, Shield, defend-deactivating tumor trgeting T cells that ATTACK the immune system
  2. Immune system to TREAT the cancer
  3. Monotherapy – anti PD1/PD-L1: Antagonist activity
  4. Evading immune response: prostate, colcn
  5. MMR deficiency
  6. Nivolumab in relaped/Refractory HODGKIN LYMPHOMAS – over expression of PD-L1 and PDL2in Lymphomas
  7. 18 month survival better with Duv in Lung cancer stage 3 – anti PD-1- adjuvant therapy with broad effectiveness
  8. Biomarkers for pD-L1 Blockage
  9. ORR higher in PD-L1
  10. Improve Biomarkers: Clonality of T cells in Tumors
  11. T-effector Myeloid Inflammation Low – vs Hogh:
  12. Biomarker Model: Neoantigen burden vs Gene expression vs CD8+
  13. Tissue DIagnostic Labs: Tumor microenveironmenr
  14. Microbiome
  15. Combination: Nivo vs Nivo+Ipi is superior: DETERMINE WHEN TO STOP TREATMENT
  16. 15/16 stopped treatment – Treatment FREE SURVIVAL
  17. Sequencing with Standard Therapies
  18. Brain metastasis – Immune Oncology Therapy – crosses the BBB
  19. Less Toxic regimen, better toxicity management,
  20. Use Immuno therapy TFS
  21. combination – survival must be justified
  22. Goal: to make Cancer a curable disease vs cancer becoming a CHronic disease


Closing Remarks: George Q. Daley, MD, PhD, DEAN, HMS


The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also received a Nobel Prize.

“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn’t honor more worthy recipients for the Warren Alpert Foundation Prize.”

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

“I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.  It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer.”
        -James Allison

“The award is a great honor and a wonderful recognition of our work.”
         Lieping Chen

I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion.  I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy.”
                                        -Gordon Freeman

I am extremely honored to receive the Warren Alpert Foundation Prize. I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field.”
-Tasuku Honjo

“I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.”
-Arlene Sharpe

Previous winners

Last year’s award went to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They were RodolpheBarrangou of North Carolina State University, Philippe Horvath of DuPont in Dangé-Saint-Romain, France, Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, and Virginijus Siksnys of the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

  • Tu Youyou of the China Academy of Chinese Medical Science, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor Nussenzweig, of NYU Langone Medical Center, for their pioneering discoveries in chemistry and parasitology of malaria and the translation of their work into the development of drug therapies and an anti-malarial vaccine.
  • Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of the Johns Hopkins University School of Medicine for research into neurotransmission and neurodegeneration.
  • David Botstein of Princeton University and Ronald Davis and David Hogness of Stanford University School of Medicine for contributions to the concepts and methods of creating a human genetic map.
  • Alain Carpentier of Hôpital Européen Georges-Pompidou in Paris and Robert Langer of MIT for innovations in bioengineering.
  • Harald zur Hausen and Lutz Gissmann of the German Cancer Research Center in Heidelberg for work on the human papillomavirus (HPV) and cancer of the cervix. Zur Hausenand others were honored with the Nobel Prize in Physiology or Medicine in 2008.

The Warren Alpert Foundation

Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccine’s creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.


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Koch Institute Immune Engineering Symposium on October 16 & 17, 2017, Kresge, MIT

Reporter: Aviva Lev-Ari, PhD, RN


Koch Institute Immune Engineering Symposium on October 16 & 17, 2017.


Summary: Biological, chemical, and materials engineers are engaged at the forefront of immunology research. At their disposal is an analytical toolkit honed to solve problems in the petrochemical and materials industries, which share the presence of complex reaction networks, and convective and diffusive molecular transport. Powerful synthetic capabilities have also been crafted: binding proteins can be engineered with effectively arbitrary specificity and affinity, and multifunctional nanoparticles and gels have been designed to interact in highly specific fashions with cells and tissues. Fearless pursuit of knowledge and solutions across disciplinary boundaries characterizes this nascent discipline of immune engineering, synergizing with immunologists and clinicians to put immunotherapy into practice.


Michael Birnbaum – MIT, Koch Institute

Arup Chakraborty – MIT, Insititute for Medical Engineering & Sciences

Jianzhu Chen – MIT, Koch Institute

Jennifer R. Cochran – Stanford University

Jennifer Elisseeff – Johns Hopkins University

K. Christopher Garcia – Stanford University

George Georgiou – University of Texas at Austin

Darrell Irvine – MIT, Koch Institute

Tyler Jacks – MIT, Koch Institute

Doug Lauffenburger – MIT, Biological Engineering and Koch Institute

Wendell Lim – University of California, San Francisco

Harvey Lodish – Whitehead Institute and Koch Institute

Marcela Maus – Massachusetts General Hospital

Garry P. Nolan – Stanford University

Sai Reddy – ETH Zurich

Nicholas Restifo – National Cancer Institute

William Schief – The Scripps Research Institute

Stefani Spranger – MIT, Koch Institute

Susan Napier Thomas – Georgia Institute of Technology

Laura Walker – Adimab, LLC

Jennifer Wargo – MD Anderson Cancer Center

Dane Wittrup – MIT, Koch Institute

Kai Wucherpfennig – Dana-Farber Cancer Institute

Please contact with any questions.


From: Koch Institute Immune Engineering Symposium <>

Reply-To: <>

Date: Friday, September 8, 2017 at 9:06 AM

To: Aviva Lev-Ari <>

Subject: Reminder – Register Today


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LIVE – 8/29 – CHI’s Oncolytic Virus Immunotherapy and ADOPTIVE CELL THERAPY, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA


Leaders in Pharmaceutical Business Intelligence (LPBI) Group will cover the event in


Aviva Lev-Ari, PhD, RN will be streaming live from the floor of the Sheraton Hotel in Boston on August 28 and August 29, 2017






7:00 am Registration

7:25 Breakout Discussion Groups with Continental Breakfast


8:25 Chairperson’s Opening Remarks

Matthew Mulvey, Ph.D., CEO, BeneVir Biopharm, Inc.

8:30 Rationale for Oncolytic Viruses as the Backbone of Combination Immunotherapy Regimens

Robert Coffin, PhD., Co-founder and CEO, Replimune

Oncolytic viruses (OVs) mediate anti-tumor activity through direct cell lysis and induction of host anti-tumor immunity. The ability to attract and activate T cells within the tumor microenvironment and induce interferon release suggests that OVs could be used as the backbone in combination immunotherapy strategies designed to promote anti-tumor immunity. Emerging clinical data is demonstrating significant improvement in studies of melanoma, and further clinical development for other cancers is anticipated.

9:00 FEATURED PRESENTATION: Developing Tumor-Specific Immunogene (T-Sign) Combination Immunotherapies by Arming the Oncolytic Group B Adenovirus Enadenotucirev

Brian_ChampionBrian R. Champion, Ph.D., CSO, Psioxus Therapeutics Ltd.

We have developed a broadly applicable platform system, based on the potent chimeric oncolytic adenovirus enadenotucirev (EnAd), for directing the selective localized production of a combination of immunotherapeutic agents within tumors following systemic dosing, while minimizing the potential for systemic off-target effects of such combination approaches. The presentation will highlight recent data supporting both the platform and specific T-SIGn virus candidates.

9:30 T-Stealth Technology Promotes Synergy between Oncolytic Viruses and Immuno-Stimulatory Agents

Matt_MulveyMatthew Mulvey, Ph.D., CEO, BeneVir Biopharm, Inc.

BeneVir is developing an OV platform based on T-Stealth Technology, which hides infected cells from anti-viral T-cells. This allows an OV to complete its replication program, produce progeny viruses, and spread in the tumor microenvironment despite a robust anti-viral T-cell response. In immune-competent murine tumor models, regimens that simultaneously combine immuno-stimulatory agents with T-Stealth armed OV show efficacy. However, there is no effect on tumor burden in these models when simultaneous combination regimens utilize a “Visible” OV that does not encode T-Stealth Technology. BeneVir’s lead OV will enter a Phase I trial in solid tumors in Q2 2018.

10:00 Poster Presentation: Neural Stem Cell Mediated Oncolytic Virotherapy for Ovarian Cancer

Jennifer Batalla, Graduate Student, Karen Aboody Laboratory Irell & Manella Graduate Program

10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

11:15 What Does It Take to Cure Glioblastoma; Combinations Plus?

Samuel_RabkinSamuel D. Rabkin, Ph.D., Professor, Neurosurgery, Massachusetts General Hospital and Harvard Medical School

We will discuss combination therapies for glioblastoma in representative preclinical models, involving oncolytic herpes simplex viruses (oHSV), cytokine expression, and immune checkpoint inhibitors. OHSV induce anti-tumor immunity and can be armed with therapeutic transgenes. The complex multicomponent strategy illustrates both the difficulty in treating non-immunogenic tumors and the opportunities in coupling immunovirotherapy with other immunotherapeutic approaches.

  • Oncolytic HSV (oHSV) Strategy
  1. GBM highly Immunosuppressive Cancer
  2. Impairment of MHC Class I presentation
  3. CG80, CD86 – down regulation of co-stimulatory molecule, Kb MHC I Db MHC I NKligand
  4. oHSV induces anti-tumor immunity
  5. armed with immune modulatory transgenes
  6. Immune checkpoint inhibitors can reduce immunosuppression in tumor and boost immune response
  7. Targeting Cancer Stem cells – permissive to cure – (GSC) Model (005)
  • H-Ras V12 lentiviruses; AKT act
  • TP53+/- nestin-Cre mice
  • oHSV-mCherry
  • Interferon Gamma
  • Strategy – Combination: Check inhibitors PLUS IL12 –>>> Immune response
  • oHSV G47 – Clinical trials in Japan
  • Deletion ICP6
  • IL-12 – Pro-inflammatory cytokine
  • promote proliferation of activated T- and NK cells
  • Expression on G47 delta Prolongs survival
  • Immune Checkpoint Inhibitors: PD-1;PD-L1 (bind to receptor PD-1); TCR–MHC
  • Anti CTLA-4 (Ipilimumab)
  • Strategy: anti-CTLA4+G47delta-IL12 – improve survival – cure after 80 days survival 90% by 120 days – cured mice are protected from tumor re-challenge 
  • Macropahge (Innate immune for GBM) Infiltration M! and M2
  • Triple Combination Therapy
  • Depletion of CD4 Abrogates all therapies: CD4
  • Depletion of CD8 Abrogates all therapies: CD8
  • Depletion/Inhibition abrogate Triple Therapy – Depletion ALters other Immune Cell Types: Clod – increase
  • Combination Viro-Immunotherapy: Deletion of CD 4+, CD8+ or macrophage – multiple cell types are involved and need selection for Model efficacy

11:45 Oncolytic Virus-Induced Rad51 Degradation: Synergy with Poly(Adp-Ribose) Polymerase Inhibitors in Treating Glioblastoma

Jianfang_NingJianfang Ning, Ph.D., Instructor, Neurosurgery, Massachusetts General Hospital, Harvard Medical School

Oncolytic herpes simplex virus (oHSV) sensitized glioblastoma stem cells (GSCs) to poly(ADP-ribose) polymerase inhibitors (PARPis), irrespective of their PARPi sensitivity through selective proteasomal degradation of key DNA damage response protein, Rad51, mediating the combination effects. This synthetic lethal-like interaction increased DNA damage, apoptosis, and cell death in vitro and in vivo. Combined treatment of mice bearing PARPi-sensitive or -resistant GSC-derived brain tumors greatly extended survival compared to either agent alone.

  • DNA damage response (DDR): guardian of genome maintenance
  1. DNA Demage: SIngle strand break, double strand break, bulky sdducts, base mismatch insertion/deletion, base alkalation
  2. PARP inhibition
  3. PARPi combination with anti-cancer – PARPi and oHSV increase apoptosis and DNA damage
  4. Genetic engineering of oHSV confers cancer PARPi-selectivity and PARPi-resistant GSCs
  5. Rad51
  6. oHSV inhibits HR
  7. oHSV-induces proteasomal degradation of Rad51 mediates  – Rad51-silencing abrogates the synergy between PARPi and oHSV
  8. infiltration: Intracelebral vs Intra-tumor
  9. Induction of aptosis and DNA demage in brain tumors in vivo
  10. oHSV – selective disruptor of DDR – penetrates BBB,

12:15 pm Close of Oncolytic Virus Immunotherapy


Cambridge Healthtech Institute’s 4th Annual

Adoptive T Cell Therapy

Delivering CAR, TCR, and TIL from Research to Reality
August 29 – 30, 2017 | Sheraton Boston | Boston, MA


Greater understanding of T cell biology as well as promising patient outcomes have led to immunotherapies accelerating at an unprecedented pace. With multiple engineered receptors making an impact, many biotech and pharma companies are already entering clinical trials in a race to get to market. However, with the end goal being the same – improved patient outcomes – there is still work to be done. Cambridge Healthtech Institute’s Fourth Annual Adoptive T Cell Therapy event will focus on the steps needed to deliver CAR, TCR, and TIL therapies to the patient by examining emerging science, autologous immune cell products, and allogenic immune cell products. Overall, this event will address clinical progress, case studies, and critical components to make adoptive T cell therapy work.


Final Agenda


12:00 pm Registration




1:15 Chairperson’s Opening Remarks

Kite Pharma was acquired by Gilead on 8/28/2017

1:20 Building Better T Cell Therapies: The Power of Molecular Profiling

Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics

Chimeric antigen receptor (CAR)-T cells are a promising new modality for cancer immunotherapy and many variants are rapidly being developed across the immuno-oncology space for haematological and solid tumor malignancies. The field has displayed enormous promise, however the rules governing which attributes drive efficacy are still being learned. Here, we present early insights from transcriptomic and epigenetic profiling of CAR-T cells describing how cell state may play an important role.

  • Evolution of T cells Therapy for cancer: LAK and CAR-T: TIL, NK, DLI, T reg TCR CAR (I) CAR (II)
  • Technologies:Flow cytometry, Cytokine measurement, Function, RNA expression –
  • next generation Technology: RNAseq, ATACseq, Single-cell analysis, ML, CyTOF, BigDAta algorithms
  • Outcomes
  • CAR Technology
  • T-Cell Signaling to create artificial molecules
  • Rapamycin-resistant allogenic T cells
  • T cell gene : IFN-gamma vs IL6
  • Lineage potential, differentiation cell expression T6, T12
  • T cell less well defined after CAR-T production – CHange in activation/Ag experience over the CAR-T production process
  • MST – Minimum Spanning Tree: CAR expression in sub-populations may vary in constructs with different endo-domains
  • CAR signaling may vary in construct that contain different endo-domains
  • Antigen stimulation in vitro: Extract RNA,
  • CAR Ag on T cell transcriptional profile: Process — >> Antigen Stimulation –>> Final Product, Drug Product + Ag Stimulation
  • Epigenetic profiling
  • Does cell state predict response potential?Gene accessibility vs % cytokine x hours after production completed
  • Interrogating cell state across the genome: gene regulation networks
  • Leveraging “big data”: hetegogeniety of cells and cellular types/age Hyperparameter optimization

1:50 Tricked-Out Cars, the Next Generation of CAR T Cells

Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio

Genetically-engineered CAR T cells are designed to supplement a patient’s immune system and can be further engineered to survive and overcome immune evasion mechanisms employed by tumors. We found that addition of a PI3-kinase inhibitor during manufacturing enriched for memory-like CAR T cells without complicated cell sorting procedures. These methodologies, combined with synthetic biology and gene editing, can be considered for the further development of CAR T cell technology.

  • Hme malignancy CART: anti-CD19 or anti-BCMA Cart (Promicing Targett for Multiple Myeloma (MM) cells
  • Stable disease, PR, VGPR, CR/sCR
  • Clinical response: Time to response and identification of of dose(s)
  • Overcoming solid tumor microenvironment
  • Manipulatinf T cell lineage via PI3Ki-AKT Pathway ia a Rheostat for T cell Differentiation
  • APC, CD8 – T cell Placticity self revnewal long lived vs terminal no renewal
  • Phenotypic differences in cells grown in bb007; il2, IL2 = bb007, IL-7 +IL-15 vs CyTOF
  • Comparison: Vehicle vs IL-2 culture vs IL-7 + IL-15 Culture vs IL-2 + IL-15
  • DARIC: Drug Regulated Antigen Receptor Technology
  • Genome Edit CRISPR – megaTAL Expertise: Broad range od potential protein
  • Dustructive Gene HDR – Knock0Out Gene vs Knock-IN
  • Multiplex: 3 megaTAL multiplex Editing
  • TCRalpha locus – gene editing: HDR generated CAR T cells have equiv phenotype as LV-CAR-T cells
  • Cytotoxicity vs Cytokine production
  • TGFbeta receptor – A chimeric TGF Beta receptor (CTBR) replaces endogenous
  • CTBR12 signal converter enhances activity of CAR T cells: STAT activation; Gene expression changes; Enhanced Tumor Cell Killing
  • Synthetic Biology plays a greater role

2:20 SPEAR T Cells for Solid Tumor Therapy

Mark Dudley, Ph.D., Senior Vice President, Bioprocessing, Adaptimmune

Adoptive cell transfer with gene modified T lymphocytes is effective for some advanced cancer indications. Specific peptide engineered antigen receptor (SPEAR) T cells that recognize the NY-ESO-1 cancer-testes antigen have shown promise in early phase trials for melanoma, multiple myeloma, and synovial sarcoma. Combination therapies and product improvements are being explored, and a registration trial is planned. Numerous tumor antigen candidates predicted from proteomic and HTS analysis of tumor specimen NAS have been used to generate new SPEAR T cells. T cells targeting MAGE-A10, MAGE-A4, and AFP are approved for initial evaluation in clinical trials in new solid tumor indications in 2017. A robust manufacturing platform that generates multiple SPEAR products for exploratory registration studies will be discussed. Challenges in scaling out successful autologous cell therapies and opportunities for implementing automation and improving T cell products will be assessed.

  • MAGE-A-10 TCR: ‘X-scan’ Specificity Analysis: TCR peptide recognition
  • Clinical efficacy of SSPEAR T-cells : Melanoma, synovial sarcoma and multiple myeloma
  • Antigen expression and prior lymphodepletion explored in pitol trial, results presented at ASCO 2017.
  • Open Trials: HCC, Uretrial Cancer
  • SOlid Tumors: MAGE-A4 SPEAR T-cells
  • Product supply forclinical trials
  • SPEAR T cell manufacturing: Platform process – continuous upgrade of unit operations: Apheresis, Activation and LV Trunsduction, Expansion and polarization, harvest and formulation, INFUSE
  • Media Optimization vs Programming T-Cells
  • P2: Cryopreserve: Total nucleated cells vs Days of growth in culture–>> optimal results at 14 days, One Product not like others: NYESO T-Cell expansion
  • Process 1 vs Process 2 – 80% of batches dramatic change
  • Manufacturing Lifecycle – Exploratory phase INDs: Academic vs Industry vs Pivotal/Commercial
  • Industry: CRO, CMO, Stable documented, slow change control, audit facilities and QA, scalable and transferrable
  • Pivotal/Commercial

Miltenyi_Biotec2:50 The Generation of Lentiviral Vector-Modified CAR-T Cells Using an Automated Process

Boro DropulicBoro Dropulic, Ph.D., General Manager and CSO, Lentigen Technology, Inc.

Participants will learn about: 1) How Lentiviral vectors are a proven robust technology to genetically modify cells 2) The Development of a large-scale lentiviral vector manufacturing process using a chemically defined, serum free suspension bioreactors 3) How automation using the CliniMACS Prodigy is a robust and cost effective method to generate patient specific CAR-T cells 4) The design and testing of CAR constructs – factors that influence in vivo efficacy 5) How automation provides options for the manufacture of CAR-T cell products: Centralized vs Decentralized models.

  • Lentiviral vectors (LV)
  1. Very stealth – no genotoxicity
  2. efficient transduction
  3. HIV vector, AIDS
  4. Implementation of suspention Serum-Free Chemically-dependent
  5. USA cGMP
  6. Generic and novel CD19 CAR-T LV – demonstrated target-specisif lysis in vivo, eliminated Raji tumors in vivo in mice
  7. Patients achieveing neagtive remission
  • Improving CAR-T function: Geometry and Binding – CD19
  • 4-1BB co-stimulation T-Cells: production of anti CD22 CAR-T cells
  • Dose level: Effective dose: 1×10 tot the power of 6
  • Biospecific CD19-CD20 targeting CAR T cells in Adult Leukemia – expression of primary cells
  • Tumor eliminated — >>> Tumor selected for escape –>>> analysis of escape strategy
  • POC: cell processing facilities integrate  -cell manufacturing with ANALYTICS
  • Hospital Pharmacy Annex for Apheresis & Infusion Unit
  • Vector design, Media and conditions, Isolation of beads
  • Optimal time-point for LV – T cell cultivation from patient cells: Health DOnot vs Patient material
  • T cell phynotype – 14 day phynotype
  • Cell-Factory come online in late 2017, generic products – CAR19 LV

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing



4:00 Regulatory and Scientific Considerations for Cancer Vaccines and Adoptive Cellular Immunotherapy

Graeme E. Price, Ph.D., Research Microbiologist, Gene Transfer & Immunogenicity, FDA CBER

Cell and Gene therapy including therapeutic vaccines and cellular immunotherapy products are evaluated at FDA’s Center for Biologics Evaluation and Research in the Office of Tissues and Advanced Therapies (OTAT) previously known as Office of Cellular, Tissue and Gene Therapies. I will discuss current general regulatory and scientific considerations in the regulation of therapeutic cancer vaccines and cellular immunotherapy. In addition, research activities in OTAT will be summarized.

  • Office of Tissue and Advanced Therapies ( OTAT) [Previously Office of Cellular, Tissue and Gene Theraphies]
  • Oncology Center of Excellence (OCE) – Cancer MoonShot
  • OTAT – Regulated Products
  • Cancer Vaccines and Immunotherapy Products
  • Gene Therapies and Gene Modified Cancer Vaccines and Immunotherapy Products: Vectors, Cancer Vaccines, CART
  • Biologic Agents and Adjuvants: Dendritic Cells, Tumor antigens, Antibody tumor antibody
  • Oncology Product Approval: phases
  • FDA Safety and Innovation Act (FDASIA) – law 2012
  1. Fast track designation – Eligible: (AA) (PR)
  2. (FT)
  3. Breakthrough Therapy (BT) Multidisciplinary Meeting
  4. Accelerated Approval (AA) will include Post-Marketing Requirement (PMR) for a confirmatory study: Biomarkers
  5. Priority Review (PR)
  6. Common Reasons for BTDR Denial: appropriateness
  • 21st Century Cures Act, becomes law in 12/2016. – REGENERATIVE Medicine Advanced Therapy (RMAT): 60 days to respond. RMAT Benefit Designation
  1. Adoptive T Cell Therapies – Gene modified T Cells
  2. Complex Manufacturing Process
  3. Typical CAR construct: Complex Vector Design: SIgnal 1 + SIgnal @2012pharmaceuticalCD19 IND Applications
  4. Product Characterization in Immunotherapy: demonstrate comparability, quality of growth factors and cells
  • products with multiple active components: Identity and potency – TESTING for
  • Personalized products: Autologous cancer vaccines – if not cryopreserved

CART-T Cells: Safety Issues and Concerns:

  • Cytokine Release Syndrom
  • Neurologic Toxicity +/- CRS: Cerebral edema, Infections, Long term

FDA Pilot CAR T-cell DB Project Objectives: CMC and Clinical Safety

  • If Data to small – risk can’t be assess
  • confidential data analysis
  • Identify safety trends across INDs

SOURCES on FDA Website

  • Cell and Gene Therapy Guidances


4:45 Market Access and Reimbursement for Immuno-Oncology Drugs in Today’s Healthcare System

Gergana Zlateva, Ph.D., Vice President, Payer Insights and Access, Oncology, Pfizer

Now that immunotherapies have hit the market, with the promise of more to come, the healthcare system will need to establish standards for cost and reimbursement of immuno-oncology agents. This talk will address how the healthcare marketplace can prepare for the adoption of novel pricing and reimbursement models to increase patient access to immunotherapies. Establishing the value of IO therapies to payers and HTAs will also be addressed in the context of pricing and evidence generation.

Click here for keynote biographies

  • 83% of survival gains in Cancer – attributed to treatment , including Medicines
  • In past 5 years, 22 tumor types ahve new medicines for

# of Treatment Options:

Investigational COumpounds for NSCLC: Cytotoxin, Targeted tx, Immunotherapy: Marketed, Pre/Reg, Phase III, Phase II

COST of Oncology & Supportive Care Cost Globally

  1. Efficacy, Safety, Relative Efficacy, Relative Value (Cost-Benefit Analysis), Budget Impact (# of candidates for a given budget)
  2. Value of Immuno-Oncology – Assessment:
  • Median Survival
  • long term benefit
  • utility gain post progression
  • relationships : PFS and OS: Redefined wiht OS = redefined with IO
  • FRAMEWORKS in Oncology for assessment of Cost of Treatments:
  1. ICER (Evidence Reports),
  2. OSCO Value Framework),
  3. NCCN (Evidence Blocks),
  4. DrugPricingLab (Oncology Drug Abacus), Memorial Sloan Kettering
  • OPDIVO: HTA Reimbursement Decision BY Agency By Country
  • Promise of Combination Therapies: AntiPD-1/PD-L1 MAb – Study by companion agent
  • PATIENT Perspective: Multiple Combinations, Multiple Indications, Longer Treatment, Better Chance to Fight Cancer, Increase cost of therapy
  • Putting Patient FIRST: Evidence vs Access: Stop treating decisions, Intermittent treatment, side effect mgm, adherence
  • Combination Therapy vs Standard of Care ifs different than Combination vs. Agent 1, Agent 2, Agent 3 – all the variations
  • Payers will reimburse One party not three parties – if the combination is a three drugs from three vendors
  • VALUE-Based Agreements in Oncology:
  1. Triple Aim/ Institute for HC Improvement 2008
  2. HC Services
  3. Pharmaceuticals: Financial-based
  4. Value based in the US: Medicaid Best price, Medicare part B, 340B, anti-kickback statues
  5. Specific to Oncology:
  6. PFS, OS, HR, CR – not captured in medical claims data
  7. Outcomes Agreements: Genetech – Priority Health Outcomes-Based Pilot
  • Avastin in Lung Cancer
  • Rebates tied to PFS a key endpoint in the Phase 3 PCT



5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

SC1: Bioinformatics for Immuno-Oncology and Translational Research

SC2: Microbiome in Immuno-Oncology

*Separate registration required, please click here for more information.

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LIVE – 8/28 – CHI’s 5th Immune Oncology Summit – Oncolytic Virus Immunotherapy, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA


Leaders in Pharmaceutical Business Intelligence (LPBI) Group will cover the event in


Aviva Lev-Ari, PhD, RN will be streaming live from the floor of the Sheraton Hotel in Boston on August 28 and August 29, 2017






7:30 am Registration & Morning Coffee


8:25 Chairperson’s Opening Remarks

Brian R. Champion, Ph.D., CSO, Psioxus Therapeutics Ltd.

  • Virus: Design, Selection, Pre-Clinical Testing

8:30 KEYNOTE PRESENTATION: Engineering and Bio-Selection to Optimize an Oncolytic Virus Platform

John_BellJohn Bell, Ph.D., Senior Scientist, Center for Innovative Cancer Research, Ottawa Hospital Research Institute

Oncolytic viruses are therapeutics that are designed or selected to specifically infect and destroy cancer cells. There are multiple strategies that can be employed to create viruses that replicate in and kill tumors; however, one common feature of malignant cells is that they lack a potent anti-viral response. I will discuss the molecular basis for these defects, how best to exploit them to create tumor killing therapeutics and strategies to improve manufacturing output of oncolytic viruses from manufacturing cell lines based upon these principles.

Oncolytic Viruses (OV)

  • Anti Vascular, Selective Oncolytic Replicating Cancer Gene Therapy Immune Adjuvant
  • OV selective to Tumor cells  – selectivity of OV – Cellular Anti-Viral Responses and Malignant Evolution-Incompatibilite?
  • p53, Ras, Rb, Wnt, PTEN, VPV, E6/E7, VEGF, FGF2
  • OV Therapy – exploits Cancer biology – Cellular Antiviral Responses – multiple pathologically activated Pathways
  • Bio-Selection of Optimal Oncolytic Virus Strains
  • Maraba Oncolytic Virus Platform – Rhabdovirus Structure, Life cycle, Key Features: no genotoxicity. Systemic Theraphy for Metastatic Cancer: Lang Tumours, Targeted Infection, Tumour Clearance
  • Viccinia Virus as systemic Therapeutics – PexaVec (Sillajen, Transgene)
  • How do SYStemically delivered Oncolytic Viruses ENTER tumours? – selective infection of tumor vascular EndothelialCells – response to cell proliferation
  • In ovarian cancer
  • Localized infection affects microenvironment – cytokines – nano string analysis 2 days post IV Infection — increase in PD-1 expression
  • personalized InSitu Vaccine
  • Oncolytic Herpes Virus expressing activation of T-Cells
  • Effects are Stochastic and unpredictable
  • OV — T-Cell Vaccine: COmbine principles of Vaccinology and OVTherapy
  • adivo virus  + Maraba-Tumour Ag–>> ptoduced TCell Responses: Prime Immune analysis –>> Boost immune analysis: %IFNgCD8+ T Cells – Days Post engraftment
  • Patient Heterogeniety: Immunr stimulating Activity Gene thHerapy


9:00 Tumor Selective HSV-Based Oncolytic Vectors for Treatment of GBM

Paola_GrandiPaola Grandi, Ph.D., Senior Research Director, Immunology/Virology, Oncorus, Inc.

Oncorus oHSV is controlled by certain microRNAs (miRNAs) that are present in healthy cells, but absent in cancer cells. Typically, miRNAs regulate the ability of classical messenger RNA (mRNAs) to be translated into protein or promote the degradation of mRNAs. By engineering miRNA binding sites into essential viral genes, oHSV replication and cellular destruction is prevented in healthy cells. Since cancer cells lack these specific miRNAs, Oncorus oHSV is free to replicate in and destroy them.

  • Harnessing the body’s power to fight tumors – Developing Best-in-class Next-Gen oHSV Vectors to trigger Immune response
  • Infection of Tumor cells >> Oncolysis –>>
  • Glioblastoma Multiforme: Lead Candidate -ONCR-001 – when armed with immune modulatoring payloads, shows more promising results: Vehicle: Oncorus Unarmed oHSV (matrix modification); Armed oHSV (matrix modification +xx)
  • Insertion of miR-Target Cassettes Controls Expression of Essential  Viral Genes and Payloads
  • Proof of Concept: no neurotoxicity of miR controlled virus after intracrenial injection, WT HSV-1 fatal
  • Multiple-miR Attenuation nenables pursuit of Cancer beyond Brain (Liver)
  • Robust Neurovirulence Factor: Attenuates neurotoxicity; Inhibits autophagy by binding to Beclin-1; Inhibit IDO: indirect regulation – IDO expands, recruits and activates MDSCs, converts trytophan to kynurenine production stimulated by IFNgamma
  • Targeted Viral Entry for replication – remove portion of native gD gene and insert EDFR binding domain
  • Receptor Engineering: WIld type, gD
  • EGFR retargeted vector: Tumor Volume vS Days after virus injection – Intracranial HSV injection in normal and in GBM mice
  • Enhanced Viral Spreading: Control vs EGFR-retargeted vs Matrix Modified Payload  + EGFR-retargeted (Immune Modulatory)  – TUMOUR VOLUME reduced the most for MatrixModified Payload + EGFR-retargeted
  • T-cells, NK cells,
  • ONCR-001 IND in GBM anticipated H2 2018

TD2 tagline9:30 Coffee Break

10:00 WO-12, a Multi-Mechanistic Immuno-Oncolytic Therapy

Steve_ThorneSteve H. Thorne, CSO, Western Oncolytics Ltd.

The next generation of oncolytic viruses will likely combine multiple genetic modifications (transgenes and viral genetic alteration) that act to synergistically target tumors through multiple mechanisms. In particular, approaches that (i) enhance systemic delivery and viral spread within and between tumors, (ii) activate a potent anti-tumor T-cell response, and (iii) modify the tumor microenvironment to enhance the activity of both the viral therapy and other therapies would produce additional benefits. The Western Oncolytics platform and its lead product WO-12 aim to achieve these goals. WO-12 has demonstrated enhanced activity in preclinical models and will soon enter clinical testing.

  • 2015 IMLYGIC becomes first approved OV in US [1904 – Rabies Virus Vaccination, live non-attenuated virus Egypt 101 Virus, Cancer 1952]
  • Viral replication inhibited – Normal cell SPARED
  • Tumor Lysis – Virus spread – Vaccinia
  • Next Generation Vectors modify tumor microenvironmentaddition of transgenes can enahnce activity
  • Expression of combinations of multiple Tx transgenes and viral modifications
  • WO-12 Design – Vaccinia Virus
  1. surface deglycosylation – does not effect infectivity and reduces TLR2 ligand activation
  2. HPGD Insertion – # of anti-viral CTL after vaccination of naive BALB/c mice with different vectors: Increase in WR.TK-TRIF
  3. TRIF Insertion
  4. TK & C12L Deletions
  • Optimizing immune activation – increase systemic anti tumor CTL response while reducing anti-viral: Reduced anti-viral: Tumor Volume/days after virus
  • Re-directing TLP Activation to enhance cell mediated immune responses
  • Immunogenic cell death and IFN response leading to a primarily
  • Overcoming immunosuppression – Resistance to oncolytic virus correlates with higher @ of myeloid derived suppressor cells (MDSC) in tumor
  • Expression of murine HPGD decreases MDSC and T-regs in the Tumor
  • Targeting of PGE2
  • % Survival vs Day after Treatment and Tumor Volume vs Day of Treatment
  • Pre-clinical Efficacy – nWO-12 – Avoid antiviral Immunity and immune suppression
  • IV (intra-venous) Delivery vs IT (intra-tumor) Delivery

10:30 Pepticrad, a Novel Oncolytic Virus-Based Therapeutic Cancer Vaccine

Sari_PeseonenSari Pesonen, Vice President, Clinical Development, Valo Therapeutics, Finland

PeptiCRAd (Peptide-coated Conditionally Replicating Adenovirus) is an innovative and unique way of combining two clinically proven cancer immunotherapy approaches: an oncolytic adenovirus and a cancer-specific peptide vaccine, to take advantage of the best features of both technologies. The idea is straightforward: to use immunogenic virus as active carrier of tumor-specific peptides to direct the immune system to specifically target and kill cancer cells.

  • PeptiCARd
  1. Oncolytic Adenovirus (negative charge)
  2. Tumor-specific  Peptides (positive charge)
  3. Patient-specific Treatment – OV highly immunogenic –>>> Peptide Vaccine ANti-tumor immunity is high and anti-virus immunity is low
  4. OV are potential Cancer Vaccine/Immunotherapy candidates
  • Genetic engineering for increased tumor specificity
  • hig immunogenicity may help breaking cancer-driven immune tolerance
  • limitation of OV is that they trigger a strong anti-virus immunity and only weak anti-tumor immune response in Cancer patients
  • Per-existing immunity to OV potentiates its Therapeutic efficacy
  1. Virus replication
  2. 3 of T-regs in tumor
  3. #of T-cell in Tumor
  4. # CD4, CD8
  • PeptiCRAd eradicates melanoma tumors
  • PeptiCRAd was the most effective in controlling tumorgrowth >> induced high # of tumor peptide – presenting mature dendritic cells
  • induced systemic tumor-specific CD8+
  • targeting two antigens provides better anti-tumor efficacy
  • Tumor Volume/days after treatment: PeptiCARd (TRP-2 – best efficacy
  • Phase I Clinical Trial with PeptiCRAd – selected indications and checkpoint inhibitor (CPI) combination
  1. Triple negative BR CA
  2. Malignant Melanoma
  3. NSCLC
  • CPI show clinical activity in PT with ongoing anti-tumor immune response
  • local treatment with OV attracts T-cells — Intra-Tumor (IT) OV delivery is superior to systemic route (IV/IA (intra-arterial))


11:00 Synthetic Virology: Modular Assembly of Designer Viruses for Cancer Therapy

Clodagh_OSheaClodagh O’Shea, Ph.D., Howard Hughes Medical Institute Faculty Scholar; Associate Professor, William Scandling Developmental Chair, Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies

Design is the ultimate test of understanding. For oncolytic therapies to achieve their potential, we need a deep mechanistic understanding of virus and tumor biology together with the ability to confer new properties. To achieve this, we have developed combinatorial modular genome assembly (ADsembly) platforms, orthogonal capsid functionalization technologies (RapAd) and replication assays that have enabled the rational design, directed evolution, systematic assembly and screening of powerful new vectors and oncolytic viruses.

  • Future Cancer therapies to be sophisticated as Cancer is
  • Targer suppresor pathways (Rb/p53)
  • OV are safe their efficacy ishas been limited
  • MOA: Specify Oncolytic Viral Replication in Tumor cells Attenuate – lack of potency
  • SOLUTIONS: Assembly: Assmble personalized V Tx fro libraries of functional parts
  • Adenovirus – natural & clinical advantages
  • Strategy: Technology for Assmbling Novel Adenovirus Genomes using Modular Genomic Parts
  • E1 module: Inactives Rb & p53
  • core module:
  • E3 Module Immune Evasion Tissue targeting
  • E4 Module Activates E2F (transcription factor TDP1/2), PI3K
  • Adenovirus promoters for Cellular viral replication __ Tumor Selective Replication: Novel Viruses Selective Replicate in RB/p16
  • Engineering Viruses to overcome tumor heterogeneity
  • Target multiple & Specific Tumor Cel Receptors – RapAd Technology allows Re-targeting anti Rapamycin – induced targeting of adenovirus
  • Virus Genome: FKBP-fusion FRB-Fiber
  • Engineer Adenovirus Caspids that prevent Liver uptake and Sequestration – Natural Ad5 Therapies 
  • Solution: AdSyn335 Lead candidat AdSyn335 Viruses targeting multiple cells
  • Engineering Mutations that enhanced potency
  • Novel Vector: Homes and targets
  • Genetically engineered PDX1 – for Pancreatic Cancer Stroma: Early and Late Stage

11:30 Adenovirus-based virotherapy for disseminated disease

David T. Curiel, MD, PhD., Distinguished Professor of Radiation Oncology, D=rector, Biologic Therapeutics Center, Washington University

Effective virotherapy for disseminated neoplastic disease required precise =umor targeting. The unique molecular plasticity of adenovirus offers the p=tential to achieve the tumor selectivity required for virotherapy for meta=tatic disease.

  • OV for DIsseminated Neoplastic DIsease
  • Vector Targetinc:
  1. Restrict gene expression
  2. mitigate liver sequestration
  3. Transduction Targeting – integrin binding ligand capsid protein hexon HVR7 Chimerism basis of vector PLUS Transcriptional Targeting works synergistic – modification of Adenovirus Fiber Protein
  4. Replacement of Adenovirus Fiber with T4 Fibritin – Caspid dysthesis AdB2 cmvLuc
  5. Camelid sdAb Retargeting of Adenovirus – A robust technology CRAd-Based Tumor Selectivity
  6. Targeting Tumor cutotoxicity

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Session Break


1:25 Chairperson’s Remarks

Fares Nigim, M.D., Massachusetts General Hospital and Harvard Medical School

1:30 Stroma Targeting Strategies for Oncolytic Virotherapy

Daniel Katzman, PhD., CEO, Unleash Immuno Oncolytics

  • Clinical Trials: OV in Clinical Development – 35 Trials Meyer Oncology 2017
  • Malignant Cells + Tumor Associated Stromal Cells
  • normal stroma are different thn Tumor activated stromaLateralization
  • SPARC is overexpressed in malignant and tumor associated stromal cells
  • SPARC is a key regulator of proliferation
  • number Cell type E4 copies ng DNA ratio/Hours after viral infection or /Days post injection

2:00 Development of OV Immunotherapy Using a Novel Preclinical GBM Model

Hiroshi_NakashimaHiroshi Nakashima, Ph.D., Instructor, Neuroscience, Brigham and Women’s Hospital

Mechanism of action of the Oncolytic virus includes direct tumor killing and vaccine adjuvant. Since OV immunotherapy is emerge to apply in incurable glioblastoma multiforme (GBM) for the durable therapeutic effects, our new glioma mouse model will provide new opportunity to evaluate the combined OV therapies that work under the patient-mimicked immunological condition.

  • Immunotherapy for TX of GBMs: Controlled Neurovirulence, defective to generate DNA resource
  • Next generation of oHSV: Efficacy and Safety – GADD34 enhances expression
  • Combination CheckPoint – PD-1 Aband OV: Tumor progression with T-Cell exhaustion Pro-tumor immunity- specific to tumor-antigen can mimic disease condition in GBM Patients
  • and the timing of Immunotherapy in GBM models
  • Antigen exposure & Tumor Growth: Acute infection, Naive, Chronic infection
  • Antigen persistence, temporal Antigen exposure, no antigen experience
  • PD-1 expression is high in brain-infiltrating GP33+ CTLs
  • Blocking PD-1 rescued mice with exhausted T-cells from GBM
  • Development of PD-1 blockade armed oHSV.
  • Cross-talk between brain-infiltrating anti- and pro-tumor immune cells
  • GP33 vs CD44
  • Limitation of PD-1 Blockade to Cure- suggesting other pre-tumor immunity contributes to suppress anti-tumor immunity

2:30 Pexa-Vec: A Multi-Mechanistic Immunotherapeutic Modulator of the Tumor Microenvironment

Naomi De Silva, Associate Director, Preclinical Science, Sillajen Biotherapeutics, Inc.

Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus, engineered to preferentially infect tumor cells, disrupt vasculature, and stimulate anti-tumor immune responses. A Phase III trial evaluating Pexa-Vec in the treatment of advanced primary liver cancer is underway.

  • Broad Tropism – Infection and uptake to multiple receptor targets
  • Vaccinia CD31 and CD8 and Granzyme B Positive in Metastatic Pancreatic Cancer – Oncolytic vaccinia targets tumor endothelial vasculature
  • Anti-tumor responses important for eradication of malignancies
  • Pexa-Vec increases T cells infiltration into tumors
  • Oncolytic Vaccinia increases PD-L1 expression
  • Combination of Oncolytic Vaccinia anf anti-PD-1 antibody decreases tumor growth
  • Pexa-Vec’s ability to induce anti-tumor immune response
  • Future study: Pexa-Vec in combination with checkpoint inhibitor CRC

TD2 tagline3:00 Refreshment Break

3:30 Designing Clinical Trials to Elucidate Oncolytic Virus Mechanisms-of-Action

Caroline_BreitbachCaroline Breitbach, Ph.D., Vice President, Translational Development, Turnstone Biologics

Oncolytic viruses have been shown to target tumors by multiple complementary mechanisms-of-action, including direct oncolysis, tumor vascular targeting and induction of anti-tumor immunity. Phase I/II clinical trials can be designed to validate these mechanisms. Development experience of an oncolytic vaccinia virus and a novel rhabdovirus oncolytic vaccine will be summarized.

  • Local effect: Cell Lysis
  • Systemic: Immune response
  • Turning Maraba (MG1) into T Cell Immunotherapy – ability to engage memory T cells to generate durable secondary immune response
  • MG1 Mechanism of DIrect T Cell Induction
  • Biology of T cell boosting:
  1. Virus infects follicualr B Cells
  2. Bcells provide virus to dendritic cells to present antigen
  3. DCT Prime – 9 days interval: Prime immune analysis
  4. DAy 14 boost induction
  5. Immune Boost in Tumor Greater in Improved Survival
  6. % survival vs days post treatment
  7. PK and viremia: Day 1,5,9,14, 11 days after dose #2
  8. Immunogenic Markers: Chemokines, Cytokines, Markers of Attack
  9. Evidence for Robust IMMUNE RESPONSE: HIGHEST RESPONDERS for self antigen
  10. Pembrolizumab Trial Design:Positive MAGE-A3 expressing tumors
  11. MG1 OV: systemic delivery and targeted metastatic tumor site


4:00 Development of an Attenuated Oncolytic Influenza a Virus Expressing Mycobacterial ESAT-6 Protein

Michael Bergmann, M.D., Ph.D., CMO, Vacthera

We have expressed ESAT-6 in a partial NS1-deletion influenza virus. ESAT-6 expressing viruses were associated with lower levels of NF-kB activating as compared to empty viral vectors. ESAT-6 expressing viruses led to higher titers in eggs up to 1010 TCID50. ESAT-6 expressing deletion viruses were still attenuated when applied to the upper respiratory tract of mice. Intra-tumoral application of virus into B16 melanoma significantly delayed tumor growth.

  • Influenza A Virus (ESAT6 expressing partial NS1 deletion virus) – Lytic, Small RNA, Stable – live virus vaccine – infection affects Trypsin cleavage site, Elastase cleavage site
  • Conditionally replicating  – tumor ablation in PKR of INF-Defective Tumors
  • Cytokine stimulation: CD14+ CD56+ CD19+
  • Cytokine – IL15 – increased Intra tumor T-Cells and NK cells
  • Virus titers are lost during purification
  • AIM: Effective virus optimized for growth, genetic stability
  • H1N1
  • TLR2 inhibits TLR signaling in pmacrophageg
  • Viral Input in ptoduction makes Oncolytics effect depend on amount of virus
  • TB Vaccine TB/FLU-04 BCG-vaccinated healthy adults – Nasal Cytokine prduction
  • Growth optimized viruses can be generated and appear to be safe – Onlcolytic influenza

4:30 Testing and Characterization of Oncolytic Viruses

Jerrod_DenhomJerrod Denham, Ph.D., Principal & Senior Consultant, Dark Horse Consulting

Testing and characterization of oncolytic viruses typically follow the current principles for the majority of gene therapy product critical quality attributes. There are specific challenges with respect to adventitious agent safety testing and viral clearance studies. This presentation will walk through examples of how these challenges were resolved.

  • Vaccinia, HSV-1, Adeno
  • Cell QA: Cell counts, viability, identity. purity, potency,safety, stability
  • Cell Production Process (CPP): Cells, virus, Plasmids, materials, equipment,settings test methods
  • Experimental design for space cintrol
  • Cell bank vs
  • cGMP: Virus Bank – Master Virus Bank,Working Virus Bank
  • Process Characterization: Mycoplasma & Endotoxin, sterility, pH, Metabolic Analysis, Viability, Vell Counts, visual inspection
  • Unit Operation: Steile filter, concentrate, polish, purify
  • Phase III: Drug substance: Formulate, bulk drug – fill & finish–>>> drug product
  • Validation of Pre-Phase 3 manufacturing
  • Clinical Lot: at least one batch: Bulk cell harvest, Final Drug Product
  • Safety testing: Bovine, Porcine virus
  • Adventitious Virus Testing: In Vitro Assay vs In Vivo Assay
  • Neutralization: Agent for Neutralization – what if it does not work? Mock product

5:00 End of Day

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