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Cambridge Healthtech Institute’s Inaugural
Target Discovery for T Cell Therapy
Next Step to Advance Immunotherapies
August 14, 2014


T cell target discovery remains one of the biggest challenges facing the immunotherapy field. With treatments becoming ready for prime-time, researchers will need to increase their discovery efforts to meet patient need and continue advancing the field. Cambridge Healthtech Institute's Inaugural Target Discovery for T Cell Therapy gathers leaders from academia and industry actively engaged in discovery and translation of novel targets for T cell immunotherapy. Experts will share strategies for chimeric antigen receptors (CARs), T cell receptors (TCRs), tumor infiltrating lymphocytes (TILs), and novel methods for novel targets. Clinical data will be showcased as well as in depth examinations of where the field is headed.


THURSDAY, AUGUST 14

8:00 am Symposium Registration & Morning Coffee

8:25 Chairperson’s Opening Remarks

Adrian BotAdrian Bot, M.D., Ph.D., Vice President, Translational Medicine, Kite Pharma, Inc.





CHIMERIC ANTIGEN RECEPTORS (CARS)


8:30 Keynote Presentation

CAR T Cells from the Mouse Cage to the Patients’ Health

Zelig EshharZelig Eshhar, Ph.D., Professor, Immunology, The Weizmann Institute of Science

This presentation will be a brief chronicle description of the pioneering of the CAR strategy and its emergence and evolution for adoptive cell treatment of cancer. It will focus on experimental models for cancer in experimental settings and summarize the lessons learned from such models. The potential and challenges for cancer therapy in patients will also be discussed. Finally, the pioneering of the CAR strategy and its emergence and evolution for adoptive cell treatment of cancer will be outlined.


9:00 CAR T Cell Therapy: Target Antigen Discovery and Clinical Translation

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

This talk will emphasize the importance of tumor antigen discovery in the selection of targets in CAR T cell therapy. As examples, I will compare and contrast Her2/neu and EGFRvIII as solid tumor targets. I will also discuss the clinical translation of these two CAR-based therapies.


9:30 Clinical Responses in Patients Infused with T Lymphocytes Redirected to Target Κ-Light Immunoglobulin Chain

Carlos A. RamosCarlos A. Ramos, M.D., Assistant Professor, Medicine, Section of
Hematology-Oncology, Baylor College of Medicine

T cells expressing chimeric antigen receptors (CARs) targeting B-cell¬ malignancies show remarkable clinical efficacy but their long term persistence causes depletion of normal B cells and hypogammaglobulinemia because the antigens targeted do not discriminate tumor from normal B cells. Since B-cell malignancies express either a κ or a λ-light immunoglobulin we generated a CAR (κ.CAR) specific for κ-light chain to selectively target κ+ lymphoma/leukemia cells, while sparing the normal B cells expressing the non-targeted λ-light chain. We present results of a phase I clinical of T cells express

10:00 Coffee Break


T CELL RECEPTORS (TCRS)

10:30 Expression of Cancer Testis Antigens in Human BRCA-Associated Breast Cancers: Potential Targets for Immunoprevention

Achim A. JungbluthAchim A. Jungbluth, M.D., Ph.D., Director, Immunohistochemistry, Pathology, Memorial Sloan-Kettering Cancer Center

Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets that are expressed in early cancers, but absent in normal breast epithelium of these high-risk individuals, could provide the basis for the development of effective immunoprophylactic strategies. Cancer testis (CT) antigens are potential candidates because their expression is restricted to tumors, and accumulating data suggest that they play important roles in cellular proliferation, stem cell function, and carcinogenesis.

11:00 Target Discovery for TCR-Mediated Immunotherapy of Cancer with ImmTACs

Emma HickmanEmma Hickman, Ph.D., Head, Target Validation, Immunocore

ImmTACs are bi-specific, pico-Molar affinity T cell Receptors fused to an anti-CD3 specific scFv that re-directs a potent T cell response towards its target. The most advanced ImmTAC reagent to-date, IMCgp100, is well tolerated in melanoma patients and induces T cell mobilisation and tumour shrinkage in clinical trials. Here we discuss our approach to target identification and target profiling for the ImmTAC platform.

11:30 Fine-Tuning TCR-Antigen Specificity and Predicting Potential Off-Target Reactivity

Joanna E. BrewerJoanna E. Brewer, Ph.D., Group Leader, Cellular Biology, Adaptimmune Ltd.

Adoptive T cell therapy (ACT) with gene-modified T cells isemerging as a highly promising strategy forthe treatment of many types of cancer. Mutating T cell receptors, to improve their affinity for tumour specific epitopes,provides the needed potency for efficacy but may present safety concerns for off-target recognition as TCRs effectively bypass thymic selection. A combination of peptide bioinformatics and primary cell screening offers a robust delineation of any possible peptide epitopes that can be recognised by an individual TCR.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


TUMOR-INFILTRATING LYMPHOCYTE (TIL) THERAPY

1:30 Emerging Biomarker Approaches to Predict Response in Melanoma T Cell Therapy

Laszlo RadvanyiLaszlo Radvanyi, Ph.D., Professor, Melanoma Medical Oncology, University of Texas, MD Anderson Cancer Center

The high clinical response rates (up to 50%) in melanoma patients receiving autologous tumor-infiltrating lymphocyte (TIL) therapy offers us an unprecedented opportunity to identify both on-treatment and predictive immunotherapy biomarkers. This talk will present our work on a comprehensive systems biology platform identifying biomarkers of response and resistance in a diverse array of specimen types from patients receiving TIL therapy. A number of TIL phenotypic markers and genomic markers in tumors predictive of response and improved survival after therapy have been identified; these markers also beginning to shed light on the mechanisms underlying therapy resistance.

2:00 Developing Potent Cancer Therapies Targeting Cancer Germline and Mutated Antigens

Paul F. RobbinsPaul F. Robbins, Ph.D., Head, DNA Sequencing and FACS Cores, Surgery Branch; Staff Scientist, Center for Cancer Research, National Cancer Institute

Current cancer gene therapy trials have focused on transducing autologous T cells with T cell receptors (TCRs) that recognize tumor antigens with limited or no normal tissues expression, as severe toxicities were observed in clinical trials targeting differentiation antigens. In a recent trial utilizing a TCR directed against the cancer germline antigen NY-ESO-1, whose expression is limited to the normal testis, objective clinical response rates of 58 and 56% were observed in patients with melanoma and synovial cell sarcoma, respectively, but no normal tissue toxicities attributed to the transferred T cells were observed. Additional strategies are also being developed to target mutated epitopes that are generally limited in their expression to a single patient but that may represent particularly potent targets for therapy.

2:30 Sponsored Presentation (Opportunity Available)

3:00 Refreshment Break


NEW METHODS TO DISCOVER NOVEL TARGETS

3:15 High-Throughput Mass-Spectrometry-Based Identification and Selection of Novel Targets for Cancer Immunotherapies

Harpreet SinghHarpreet Singh, Ph.D., Managing Director, CSO, Co-Founder, Immatics Biotechnologies GmbH

The XPRESIDENT® antigen discovery platform (also known as the Tuebingen Approach) allows the rapid identification, selection and validation of novel T cell targets which have been discovered with a combination of mass-spectrometry based quantitative peptidomics, transcriptomics, T cell immunology and bioinformatics. Also data from several clinical trials conducted with these targets as vaccines in several hundreds of patients and their suitability for adoptive cellular therapy will be discussed.

3:45 In vivo Discovery of Targets for Cancer Immunotherapy

Kai W. WucherpfennigKai W. Wucherpfennig, M.D., Ph.D., Cancer Immunology & AIDS, Dana-Farber Cancer Institute; Professor of Neurology at Harvard Medical School

A novel pooled shRNA screen has been developed to discover genes that represent key negative regulators of cytotoxic T cell function in tumors. shRNAs that target such negative regulators greatly enhance T cell accumulation in tumors and improve T cell function. This approach enables systematic target discovery in relevant tissue microenvironments.

4:15 Chairperson’s Closing Remarks

Adrian Bot, M.D., Ph.D., Vice President, Translational Medicine, Kite Pharma, Inc.

4:30 Close of Symposium