Leaders in Pharmaceutical Business Intelligence (LPBI) Group

1:15 – 3:15 8/30 TUMOR NEOANTIGENS FOR PERSONALIZED IMMUNOTHERAPY @IMMUNO-ONCOLOGY SUMMIT – AUGUST 30-31, 2016 | Marriott Long Wharf Hotel – Boston, MA

http://www.immuno-oncologysummit.com/uploadedFiles/Immuno_Oncology_Summit/Agenda/16/2016-The-Immuno-Oncology-Summit-Brochure.pdf

 

 

Leaders in Pharmaceutical Business intelligence (LPBI) Group covers in Real Time the IMMUNO-ONCOLOGY SUMMIT using Social Media

Aviva Lev-Ari, PhD, RN,

Founder, LPBI Group & Editor-in-Chief

http://pharmaceuticalintelligence.com

Streaming LIVE @ Marriott Long Wharf Hotel in Boston

Curation of Scientific Content @Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

 

1:15 – 5:00 8/30 TUMOR NEOANTIGENS FOR PERSONALIZED IMMUNOTHERAPY

1:15 Chairperson’s Opening Remarks

Pramod K. Srivastava, M.D., Ph.D., Professor, Immunology and Medicine, Director, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut School of Medicine

• Increased cancer incidence in immunosuppred transplant patients 25 times more risk for cancer

1. Tumor immunity – if you immunize a mouth, tumor will not occur or regress or not progress
2. Tumor are antigenically distinct
3. errors in replication cand tumor sell divide
4. identical normal cells sameness to individuality Normal >> Tumor >> Neoepitopes few Neoepitope becomes mutant
5. 199502006Reponse to Mage correlate with better prognosis — all clinical trials FAILED
6. Immune response to Neoepitopes – not clear cut

1:20 Basics of Personalized Immunotherapy: What Is a Good Antigen?

Pramod K. Srivastava, M.D., Ph.D., Professor, Immunology and Medicine, Director, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut School of Medicine The definition of host-protective immunogenic antigen(s) of any human cancer of non-viral origin is still an enigma. New approaches in cancer genomics and bioinformatics are now offering a plethora of candidate antigens, whose role in cancer immunity, and specifically in host-protective cancer immunity, is under extensive testing. Outlines of some broad rules are emerging and some of these shall be discussed.

• Likelihood of being proteasomally processed MHC I binding affinity
• 1994 affinity threshold 50nM
• equivalent : Affinity -. difference self .. checkpoint blockade
• Testing the tumor-protective immunogenicity of neo-epitopes: Tumor
• Score of binding of mutant Is there tolerance to these – difference from self is a predictor of affinity – DAI score of difference
• CD8- dependence of neo-epitope-elicited cancer immunity
• Differential of Testing the tumor-protective immunogecity of neo-epitopes
• Other tumor models: tumor rejection and low affinity
• Immunological microenvironment
• strong affinity in combination with CTLA4 – Tumore rejection by some epitopes not by others
• CTLA4 blockade – CHeckpoint or T re inhibition
• Strong influence of T regs on the neoepitope repertoire of a tumor
• Immune response to neoepitope may: MHC I – peptide affinity, minor player in definition of effectiveness of neoepitopes
• Epithelial ovarian cancer Stage III/IV and T cell response – Phase I

Questions

• mutated epitope in melanoma – MHC 1 is important
• CD4 affinity

 

1:50 Novel Antibodies against Immunogenic Neoantigens

Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.

Two novel antibodies, NEO-102 (ensituximab) and NEO- 201, were developed from an allogeneic colorectal cancer vaccine that had previously shown activity in patients with metastatic colorectal cancer This vaccine was derived from an immunogenic component of the cell membrane from pooled surgical specimens from both primary and metastatic colon cancer. Patients who benefited from the vaccine in the prior clinical trial produced and sustained high levels of serum IgG against the vaccine. Several thousand candidate antibodies were screened against this vaccine and NEO- 102 and NEO-201 were candidates that demonstrated the ability to bind to colon cancer vs. normal tissue.

• solid tumor studies: tumor specific monoclonal
• Only Human Derived & Human Tested Pltform to Create Novel Therapeutics

1. patient-derived tumor samples –>> prepararion of cancer vaccince –> anti-cancer vaccine – molecular weight – are these components immunogenic –.. Production of anti-cancer-specific monoclonal antibodies –.. testing and development of mAbs –.. Hollinshead’s clinical testing of anti-cancer vaccines
2. Human screening to select active vaccine
3. Mount IgG response to the Vaccine — colorectal cancer
4. immune response – 10,00 – 3 sensicitivy
5. NEO -102 – Pancreatic cancer – novel monoclonal antibody MUCSAC – no Ensituximab binding –>> Novel mucin trget
6. anti tumor activity of a novel mAb NEO-102 optimize for regorgnition of antigens
7. antibody dependent cell cytotoxicity –
8. Tumor-specific ANtigen (TSA)
9. Phase I and Phase II – monotherapy completed
10. Phase 3 Regorafanib doses: 1.5 mg/Kg
11. 3 mg/Kg – hyperbilirubinemia – Liver mestastasis Patients, hemolysis, anemia, N&V
12. Affinity correlates with immune activity
13. 30% of Panceratic Cancer pt receive FOLFIRINX as front line therapy, and Gemcitabine/Abraxane as 2nd line.
14. New Trial: Gemcitabine/ .. NabPaxital –.. NEO-102
15. NEO-201 (h16C3) mAb – CEACAM-5, CEACAM-6

Biological way as Novel Immunotherapy

2:20 PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

Luis Alberto Diaz, M.D., Associate Professor, Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Somatic mutations have the potential to encode “non-self” immunogenic antigens. Tumors with a large number of somatic mutations due to mismatch-repair defects appear to be highly susceptible to immune checkpoint blockade. This presentation will summarize the clinical and genomic data of using mutations as neoantigens.

• Mismatch repair tumor – colon cancer – genetic and Epigenetic defects in mismatch repair 15% carcinomas across all stages 
• mutagen associated tumor
• sporadic solid tumors (colon cancer)
• pediatric tumors
• liquid tumors

Background

• Tx of tumor
• Colorectal cancers vs Non-Colorectal Cancers
• Cohort: A, B, C Autoimmune events

Biochemical Response (CEA): Merck Kyrdura,, single agent

1. MMR-proficient CRC – low tumor burden – 12 patients 
2. MMR-deficient CRC – HIGH Tumor burden – 12 patients
3. % change from baseline

Summary

% change from Baseline = Mismatch in genomic vs Histology independence

Mutation Burden va Response to PD-1 Blockade

• Mutations per Genome vs % Objective Response Rate 

Future direction

• Markers in genomics not tissue origin
• Molecular etiology of primary and secondary resistance in MRD tumors with PD-1 blockade
• kidney cancer non-Hodgkis Lynphona – low tumor burden: mismatch mutation burden,  virus
• Melanoma & Lunf Cancers: Mutagen Associated tumors

 

2:50 In situ Vaccination for Lymphoma

Joshua Brody, M.D., Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai

Prior ex vivo combinations of dendritic cells (DC) with tumor antigens have yielded immunologic and clinical responses. Intratumoral immunomodulation may bypass the need for ex vivo production of vaccine. In situ vaccination combines: intratumoral Flt3L to recruit DC, low dose radiotherapy to load DC with tumor antigens, and intratumoral TLR agonist to activate tumor-antigen-loaded DC. Preliminary results demonstrate DC recruitment and activation, systemic tumor regressions, and induction of neoantigen specific CD8 T cell responses after vaccination.

• TLR9a-based insitu vaccine – convert tumor into vaccine-manufacturing facility
• B cell lymphona – Keppa expression treated by CpG – rediation
• induction antitumor immunity by anti-tumor T-cells
• CD8 vs IFNgamma
• CD137 vs CD 45RO – memory cells: pre and post
• Flt3L-primed in situ vaccine on dendritic cells + poly-IC – vaccine activate T-cells
• 60 patients

1. Pre-rx, Pre-vaccine
2. post Flt3L Post- Vaccine
3. post-poly-ICLC (agonist)

Flt3L immune repertoire effects with CyTOF – pre-Flt3L

• In site vaccine: cellular and molecular Mechanism
• T cells, Macrophages, Ly6chi, mono, Dendritic Cells
• pIC +antiPD1

Is there a Better AIXS than PD/PD-L1?

• YES – Just EGFP Dealth Inducing CD8 T cells = JEDI
• YES  – Targeted (CRISPR) approach – 600 genes on Receptor “3”
• CRISPR discovers PD-L1 spiked in with preferential – Edit and induce genes: Library of 600 genes – PD1 is in the library
• GFP vs MHC-1 vs Jedi T cells
• Kill-able lymphoma vs resistant lymphoma
• more Dendritic cella with intratumoral than systemic Flt3L <<– has highest % of living cells

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

4:00 PLENARY KEYNOTE SESSION See Keynotes for details.

4:00 A New Era of Personalized Therapy: Using Tumor Neoantigens to Unlock the Immune System

Matthew J. Goldstein, M.D., Ph.D., Director, Translational Medicine, Neon Therapeutics, Inc. Neon Therapeutics, Inc. launched in 2015 to focus on advancing neoantigen biology to improve cancer patient care. A neoantigen-based product engine will allow Neon to develop further treatment modalities including next-generation vaccines and T cell therapies targeting both personalized as well as shared neoantigens. The company’s first trial will launch later this year investigating the combination of a personalized, vaccine with nivolumab in advanced Melanoma, NSCLC, and Bladder Cancer.

4:30 Emerging Innate Immune Targets for Enhancing Adaptive Anti-Tumor Responses

Michael Rosenzweig, Ph.D., Executive Director, Biology-Discovery, IMR Early Discovery, Merck Research Laboratories Novel cancer immunotherapies targeting T cell checkpoint proteins have emerged as powerful tools to induce profound, durable regression and remission of many types of cancer. Despite these advances, multiple studies have demonstrated that not all patients respond to these therapies, and the ability to predict which patients may respond is limited. Harnessing the innate immune system to augment the adaptive anti-tumor response represents an attractive target for therapy, which has the potential to enhance both the percentage and rate of response to checkpoint blockade.

5:00 Reading Tea Leaves: The Dilemma of Prediction and Prognosis in Immunotherapy

Morganna Freeman, D.O., Associate Director, Melanoma & Cutaneous Oncology Program, The Angeles Clinic and Research Institute With the rapid expansion of immunotherapeutics in oncology, scientifically significant advances have been made with both the depth and duration of antitumor responses. However, not all patients benefit, or quickly relapse, thus much scientific inquiry has been devoted to appropriate patient selection and how such obstacles might be overcome. While more is known about potential biomarkers, accurate prognostication persists as a knowledge gap, and efforts to bridge it will be discussed here.