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Archive for the ‘mRNA platform in Drug DIscovery’ Category


TWEETS by @pharma_BI and @AVIVA1950 at #IESYMPOSIUM – @kochinstitute 2019 #Immune #Engineering #Symposium, 1/28/2019 – 1/29/2019

 

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

 

eProceedings for Day 1 and Day 2

LIVE Day One – Koch Institute 2019 Immune Engineering Symposium, January 28, 2019, Kresge Auditorium, MIT

https://pharmaceuticalintelligence.com/2019/01/28/live-day-one-koch-institute-2019-immune-engineering-symposium-january-28-2019-kresge-auditorium-mit/

 

LIVE Day Two – Koch Institute 2019 Immune Engineering Symposium, January 29, 2019, Kresge Auditorium, MIT

https://pharmaceuticalintelligence.com/2019/01/29/live-day-two-koch-institute-2019-immune-engineering-symposium-january-29-2019-kresge-auditorium-mit/

 

 

  1. AMAZING Conference I covered in Real Time

  2. Aviv Regev Melanoma: malignant cells with resistance in cold niches in situ cells express the resistance program pre-treatment: resistance UP – cold Predict checkpoint immunotherapy outcomes CDK4/6 abemaciclib in cell lines

  3. Aviv Regev, a cell-cell interactions from variations across individuals Most UC-risk genes are cell type specificVariation – epithelial cell signature – organize US GWAS into cell type spec

  4. Diane Mathis Age-dependent Treg and mSC changes – Linear with increase in age Sex-dependent Treg and mSC changes – Female Treg loss in cases of Obesity leading to fibrosis Treg keep IL-33-Producing mSCs under rein Lean tissue/Obese tissue

  5. Martin LaFleur Loss of Ptpn2 enhances CD8+ T cell responses to LCMV and Tumors PTpn2 deletion in the immune system enhanced tumor immunity CHIME enables in vivo screening

  6. Alex Shalek Identifying and rationally modulating cellular drivers of enhanced immunity T Cells, Clusters Expression of Peak and Memory Immunotherapy- Identifying Dendritic cells enhanced in HIV-1 Elite Controllers

  7.   Retweeted

    Onward: our own Michael Birnbaum, who assures us that if you feel like you’re an immunoengineer, then you ARE one!

  8. Glenn Dranoff Adenosine level in blood or tissue very difficult to measure in blood even more than in tissue – NIR178 + PDR 001 Monotherapy (NIR178) combine with PD receptor blockage (PDR) show benefit A alone vs A+B in Clinical trial

  9. Glenn Dranoff PD-L1 blockade elicits responses in some patients: soft part sarcoma LAG-3 combined with PD-1 – human peripheral blood tumor TIM-3 key regulator of T cell and Myeloid cell function: correlates in the TCGA DB myeloid

  10. Glenn Dranoff Institute for Biomedical Research of Neurologic toxicities of CART t IL-6 activation AML – complete response – weekly dose of XmAb CD123X CD3 bispecific antibody anti tumor effect

  11. of protective HLA-DR4 effects outside of “peptide anchor” residues Class I MHC – HLA-E down regulate T and NK cells Receptor Binding: Positional preferences noted for NKG2A

  12. Yvonne Chen Activation of t Cell use CAR t Engineer CAR-T to respond to soluble form of antigens: CD19 CAR Responds to soluble CD19 GFP MCAR responds to Dimeric GFP “Tumor microenvironment is a scary place”

  13. Yvonne Chen Do we need a ligand to be a dimers? Co-expressed second-generation TGF-beta signaling

  14. Yvonne Chen “Engineering smarter and stronger T cells for cancer immunotherapy” OR-Gate cause no relapse – Probing limits of modularity in CAR Design Bispecific CARs are superior to DualCAR: One vs DualCAR (some remained single CAR)

  15.   Retweeted

    Ending the 1st session is Cathy Wu of detailing some amazing work on vaccination strategies for melanoma and glioblastoma patients. They use long peptides engineered from tumor sequencing data.

  16.   Retweeted

    Some fancy imaging: Duggan gives a nice demo of how dSTORM imaging works using a micropatterend image of Kennedy Institute for Rheumatology! yay!

  17.   Retweeted

    Lots of interesting talks in the second session of the – effects of lymphoangiogenesis on anti-tumor immune responses, nanoparticle based strategies to improve bNAbs titers/affinity for HIV therapy, and IAPi cancer immunotherapy

  18.   Retweeted

    Looking forward to another day of the . One more highlight from yesterday – from our own lab showcased her work developing cytokine fusions that bind to collagen, boosting efficacy while drastically reducing toxicities

  19.   Retweeted

    Members of our cell therapy team were down the street today at neighboring for the presented by .

  20.   Retweeted

    He could have fooled me that he is, in fact, an immunologist!

  21.  
  22.   Retweeted

    Come and say Hi! ACIR will be back tomorrow at the Immune Engineering Symposium at MIT. Learn more at . . And stay tuned to read our summary of the talks on Feb 6.

  23. Facundo Batista @MGH # in BG18 Germline Heavy CHain (BG18-gH) High-mannose patch – mice exhibit normal B cell development B cells from naive human germline BG18-gH bind to GT2 immunogen

  24. Preeti Sharma, U Illinois T cell receptor and CAR-T engineering TCR engineering for Targeting glycosylated cancer antigens Nornal glycosylation vs Aberrant Engineering 237-CARs libraries with conjugated (Tn-OTS8) against Tn-antigend In vitro

  25. Bryan Bryson Loss of polarization potential: scRNAseq reveals transcriptional differences Thioredoxin facilitates immune response to Mtb is a marker of an inflammatory macrophage state functional spectrum of human microphages

  26. Bryan Bryson macrophage axis in Mycobacterium tuberculosis Building “libraries” – surface marker analysis of Microphages Polarized macrophages are functionally different quant and qual differences History of GM-CSF suppresses IL-10

  27. Jamie Spangler John Hopkins University “Reprogramming anti-cancer immunity RESPONSE through molecular engineering” De novo IL-2 potetiator in therapeutic superior to the natural cytokine by molecular engineering mimicking other cytokines

  28. Jamie Spangler JES6-1 Immunocytokine – inhibiting melanoma Engineering a Treg cell-biased immunocytokine double mutant immunocytokine shows enhanced IL-2Ralpha exchange Affinity De Novo design of a hyper-stable, effector biased IL-2

  29. , Volume Five: in of Cardiovascular Diseases. On com since 12/23/2018

  30. Michael Dustin ESCRT pathway associated with synaptic ectosomes Locatization, Microscopy Cytotoxic T cell granules CTLs release extracellular vescicles similar to T Helper with perforin and granzyme – CTL vesicles kill targets

  31. Michael Dustin Delivery of T cell Effector function through extracellular vesicles Synaptic ectosome biogenisis Model: T cells: DOpamine cascade in germinal cell delivered to synaptic cleft – Effector CD40 – Transfer is cooperative

  32. Michael Dustin Delivery of T cell Effector function through extracellular vesicles Laterally mobile ligands track receptor interaction ICAM-1 Signaling of synapse – Sustain signaling by transient in microclusters TCR related Invadipodia

  33. Mikael Pittet @MGH Myeloid Cells in Cancer Indirect mechanism AFTER a-PD-1 Treatment IFN-gamma Sensing Fosters IL-12 & therapeutic Responses aPD-1-Mediated Activation of Tumor Immunity – Direct activation and the ‘Licensing’ Model

  34. Stefani Spranger KI Response to checkpoint blockade Non-T cell-inflamed – is LACK OF T CELL INFILTRATION Tumor CD103 dendritic cells – Tumor-residing Batf3-drivenCD103 Tumor-intrinsic Beta-catenin mediates lack of T cell infiltration

  35. Max Krummel Gene expression association between two genes: and numbers are tightly linked to response to checkpoint blockage IMMUNE “ACCOMODATION” ARCHYTYPES: MYELOID TUNING OF ARCHITYPES Myeloid function and composition

  36. Noor Momin, MIT Lumican-cytokines improve control of distant lesions – Lumican-fusion potentiates systemic anti-tumor immunity

    Translate Tweet

  37. Noor Momin, MIT Lumican fusion to IL-2 improves treatment efficacy reduce toxicity – Anti-TAA mAb – TA99 vs IL-2 Best efficacy and least toxicity in Lumican-MSA-IL-2 vs MSA-IL2 Lumican synergy with CAR-T

  38.   Retweeted

    excited to attend the immune engineering symposium this week! find me there to chat about and whether your paper could be a good fit for us! 🦠🧬🔬🧫📖

  39.   Retweeted

    Bob Schreiber and Tyler Jacks kicked off the with 2 great talks on the role of Class I and Class II neo-Ag in tumor immunogenicity and how the tumor microenvironment alters T cell responsiveness to tumors in vivo

  40.   Retweeted

    Scott Wilson from gave a fantastic talk on glycopolymer conjugation to antigens to improve trafficking to HAPCs and enhanced tolerization in autoimmunity models. Excited to learn more about his work at his faculty talk!

  41. AMAZING Symposinm

  42.   Retweeted

    Immune Engineering Symposium at MIT is underway!

  43.   Retweeted

    ACIR is excited to be covering the Immune Engineering Symposium at MIT on January 28-29. Learn more at .

  44. Tyler Jacks talk was outstanding, Needs be delivered A@TED TALKs, needs become contents in the curriculum of Cell Biology graduate seminar as an Online class. BRAVO

  45.   Retweeted

    Here we go!! Today and tomorrow the tippity top immunologists converge at

  46.   Retweeted

    Exciting start to this year’s Immune Engineering Symposium put on by at . A few highlights from the first section…

  47. Stephanie Dougan (Dana-Farber Cancer Institute) Dept. Virology IAPi outperforms checkpoint blockade in T cell cold tumors reduction of tumor burden gencitabine cross-presenting DCs and CD8 T cells – T cell low 6694c2

  48. Darrell Irvine (MIT, Koch Institute; HHMI) Engineering follicle delivery through synthetic glycans: eOD-60mer nanoparticles vs Ferritin-trimer 8-mer (density dependent)

  49. Darrell Irvine (MIT, Koch Institute; HHMI) GC targeting is dependent on complement component CIQ – activation: Mannose-binding lectins recognize eOD-60mer but not eOD monomer or trimers

  50. Melody Swartz (University of Chicago) Lymphangiogenesis attractive to Native T cells, in VEGF-C tumors T cell homing inhibitors vs block T cell egress inhibitors – Immunotherapy induces T cell killing

  51. Cathy Wu @MGH breakthrough for Brain Tumor based neoantigen-specific T cell at intracranial site Single cells brain tissue vs single cells from neoantigen specific T cells – intratumoral neoantigen-specific T cells: mutARGAP35-spacific

  52. Cathy Wu (Massachusetts General Hospital) – CoFounder of NEON Enduring complete radiographic responses after + alpha-PD-1 treatment (anti-PD-1) NeoVax vs IVAC Mutanome for melanoma and Glioblastoma clinical trials

  53. , U of Chicago IV INJECTION: OVAALBUMIN OVA-P(GALINAC), P(GLCNAC), SUPRESS T CELL RESPONSE Abate T cells response – Reduced cytokine production & increased -regs

  54. Interrogating markers of T cell dysfunction – chance biology of cells by CRISPR – EGR2 at 2 weeks dysfuntioning is reduced presence of EDR2 mutant class plays role in cell metabolism cell becomes functional regulator CD8 T cell

  55. Bob Schreiber (Wash University of St. Louis) Optimal CD8+ T cells mediated to T3 require CD4+ T help

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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.

SPEAKERS:

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 ki-events@mit.edu with any questions.

SOURCE

From: Koch Institute Immune Engineering Symposium <ki-events@mit.edu>

Reply-To: <ki-events@mit.edu>

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

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Reminder – Register Today

 

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On its way for an IPO: mRNA platform, Moderna, Immune Oncology is recruiting 100 new Life Scientists in Cambridge, MA

Curator: Aviva Lev-Ari, PhD, RN

 

Deals:

Moderna has now raised $1.9 billion from investors like AstraZeneca – 9% stack [AstraZeneca’s Pascal Soriot helped get that all started with a whopping $240 million upfront in its 2013 deal, which was tied to $180 million in milestones.], with another $230 million on the table from grants. In addition to the financing announcement this morning, Moderna is also unveiling a pact to develop a new Zika vaccine, with BARDA putting up $8 million to get the program started while offering an option on $117 million more to get through a successful development program.

Novel Strategy in Biotech:

in biotech. Instead of grabbing one or two new drugs and setting out to gather proof-of-concept data to help establish its scientific credibility, the company has harvested a huge windfall of cash and built a large organization before even entering the clinic. And it did that without turning to an IPO.

Pipeline include:

  • The deal with AstraZeneca covers new drugs for cardiovascular, metabolic and renal diseases as well as cancer.
  • partners filed a European application to start a Phase I study of AZD8601, an investigational mRNA-based therapy that encodes for vascular endothelial growth factor-A (VEGF-A)
  • Moderna CEO spelled out plans to get the first 6 new drugs in the clinic by the end of 2016.
  • The first human study was arranged for the infectious disease drug mRNA 1440, which began an early stage study in 2015.
  • Moderna built up a range of big preclinical partnerships.
  • CEO Bancel says the number of drugs in development has swelled to 11, with the first set of data slated to be released in 2017.
  • Moderna also plans to add about 10 drugs to the clinic by next summer,

 

SOURCES

UPDATED: Booming Moderna is raising $600M while ramping up manufacturing and clinical studies

$1.9B in: Moderna blueprints $100M facility, plans to double the pipeline after a $474M megaround

http://endpts.com/moderna-blueprints-100m-facility-plans-to-double-the-pipeline-after-a-474m-megaround/?utm_source=Sailthru&utm_medium=email&utm_campaign=Issue:%202016-09-07%20BioPharma%20Dive%20%5Bissue:7155%5D&utm_term=BioPharma%20Dive

 

Moderna Therapeutics Deal with Merck: Are Personalized Vaccines here?

Curator & Reporter: Stephen J. Williams, PhD – August 11, 2016

https://pharmaceuticalintelligence.com/2016/08/11/moderna-therapeutics-deal-with-merck-are-personalized-vaccines-here/

 

at #JPM16 – Moderna Therapeutics turns away an extra $200 million: with AstraZeneca (collaboration) & with Merck ($100 million investment)

Reporter: Aviva Lev-Ari, PhD, RN – January 13, 2016

https://pharmaceuticalintelligence.com/2016/01/13/at-jpm16-moderna-therapeutics-turns-away-an-extra-200-million-with-astrazeneca-collaboration-with-merck-100-million-investment/

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