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Cambridge Healthtech Institute’s 2nd Annual
Target Discovery for T Cell Therapy
Current and Emerging Targets for CAR, TCR, and TIL
August 27-28


Current targets for adoptive T cell therapies are limited and challenging. As a result, increased discovery efforts have been launched to continue advancing the field. At Cambridge Healthtech Institute’s Second Annual Target Discovery for T Cell Therapy, leaders from academia and industry will come together to actively engage in discovery and translation of novel targets for T cell therapy. Experts will share strategies around T cell receptors (TCR) and tumor infiltrating lymphocytes (TIL), and special attention will be given to chimeric antigen receptors (CAR). Emphasis will also be placed on discovering new targets and novel classes of targets expressed on the cell membrane and inside the cell, mainly with tumor-specific and mutated antigens. Overall, this event provides a comprehensive look at the current challenges and existing opportunities in T cell therapy target discovery.

Day 1 | Day 2 | Download Brochure | Speaker Biographies
UD: Unpublished Data | CS: Case Study 


Recommended Dinner Short Course*
Adoptive Therapy with CAR T Cells
*Separate registration required 


THURSDAY, AUGUST 27

7:30 am Registration & Morning Coffee


CHIMERIC ANTIGEN RECEPTORS 

8:10 Chairperson’s Opening Remarks

Nancy Parenteau, Ph.D., President and CSO, Verik Bio


Michael Jensen8:15 KEYNOTE PRESENTATION: ENHANCING THE SYNTHETIC IQ OF CAR T CELLS

Michael C. Jensen, M.D., Janet & Jim Sinegal Endowed Professor, Pediatrics; Adjunct Professor, Bioengineering, University of Washington School of Medicine; Joint Member, Program in Immunology, Fred Hutchinson Cancer Research Center

Dr. Jensen’s laboratory’s work focuses on T cell genetic modification for re-directing antigen specificity to tumors utilizing recent advances not only in the composition and specificity of receptor antigen recognition domains, but also the evolution of multifunctional cytoplasmic signaling domains developed for these chimeric antigen receptors (CARs) that provide dual activation and co-stimulatory signaling. His group is also investigating the context of adoptive transfer with respect to the conditioning of the recipient for enhanced T cell engraftment and expansion, the grafting of CARs on to central memory T cells having endogenous TCR specificities for viral epitopes to which the host has robust immunity, and, the provision tumor microenvironment survival capabilities.


9:00 GoCAR-T™ and CIDeCAR™-enabled T Cell Immunotherapy: An Evolution to Gas Pedal- AND Brake-Based Approaches 

 David_SpencerDavid M. Spencer, Ph.D., CSO, Bellicum Pharmaceuticals, Inc. 

CAR-T cell approaches have seen some spectacular successes in a subset of B cell malignancies, but efficacy in solid tumors has lagged. We have developed a highly effective, novel costimulatory element, MyD88/CD40 (MC) that can be deployed with CARs as a switch (in GoCAR-T) or in the presence of our clinically validated, Caspase-9-based suicide gene, CaspaCIDe® (in CIDeCAR). This has led to durable tumor control in solid tumor models while allowing for control of toxicity. Recent data and applications will be discussed. 

9:30 CAR T Cell Therapy: Target Antigen Discovery and Clinical Translation

Richard-MorganRichard Morgan, Ph.D., Vice President, Immunotherapy, bluebird bio

The remarkable success from a number of sites using chimeric antigen receptors (CARs) to target the B cell malignancy antigen CD19 has resulted in an enormous interest in CAR-based therapies. This talk will give a brief introduction to the field with a focus on the critical aspect of tumor antigen choice and the application CAR therapies to target solid cancers.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Durable Clinical Responses upon Treatment with Chimeric Antigen Receptor (CAR)-Engineered T Cells

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

Genetic reprogramming of T cells for adoptive cell therapy showed some tantalizing clinical successes in phase 1 trials. To date, T cells genetically engineered with second generation CARs comprising CD28 or 4-1BB as co-stimulatory domains, showed high objective responses in B-cell acute lymphoblastic leukemia (B-ALL). CAR T cells can also be very effective in large cell, follicular lymphomas or chronic lymphocytic leukemia, as demonstrated by an anti-CD19 CAR product comprising a CD28 endodomain. Upon infusion, these CAR T cells expand dramatically and then decay and clear within months, thereby allowing the recovery of endogenous B cells. Thus, a major question relates to the durability of clinical responses afforded by CAR T cells. With an increasing number of patients treated and years of follow up, evidence is mounting in support of long-lasting clinical responses upon single or double treatment with CAR T cells. In addition, these accumulating data shed light on biomarkers with clinical predictive value.

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Julien-Valton
11:15 A Multidrug Resistant Engineered CAR T Cell for Allogeneic Combination Immunotherapy

Julien Valton, Ph.D., R&D Project Leader, Cellectis

When allogeneic CAR T cell infusion is considered, host versus graft and graft versus host reactions must be avoided to elicit successful antitumor activity in vivo. We propose to address these requirements through the development of multidrug resistant TCRαβ-deficient CAR T cells. We demonstrate that these engineered T cells displayed efficient antitumor activity and proliferated in the presence of drugs, currently used in clinic as preconditioning lymphodepleting regimens.

11:45 Next-Generation Chimeric Antigen Receptor-Engineered T Cells Directed at Novel Cancer Antigens

Hinrich-AbkenHinrich Abken, Ph.D., Professor, Cancer Genetics, Internal Medicine, University Hospital of Cologne

The specificity of CAR-mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available.We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR in comparison toTCR modified T cells and the impact of the CAR activation threshold on redirected T cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer.

12:15 pm Identification and Targeting of HLA/Peptide Targets Distinct to Cancerous Tissue

Hildebrand_WilliamWilliam Hildebrand, Ph.D., Chief Scientist, Pure MHC, LLC 

The immune system naturally recognizes cancer cells via human leukocyte antigen (HLA)/peptide complexes. We use a powerful HLA cancer ligand database to interrogate cancerous tissue and to identify HLA peptide complexes distinct to cancer. Our monoclonal antibodies to these HLA/cancer targets then provide a platform for the development of immunotherapies.

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

1:00 Session Break


T CELL RECEPTOR TARGETS AND PRODUCTS 

2:00 Chairperson’s Remarks

Michael Bethune, Ph.D., Postdoctoral Fellow, Laboratory of David Baltimore, Division of Biology and Biological Engineering, Caltech

CS_Icon2:05 ImmTACs: Bispecific TCR-anti-CD3 Fusions for Potent Re-Directed Killing of Cancer Cells – IMCgp100 in a PhaseI/IIa Study against Malignant Melanoma

Luise U. Weigand, Ph.D., Team Leader, Cell Biology, Immunocore Ltd.

ImmTACs are bispecific 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 to date, IMCgp100, is well-tolerated in melanoma patients and induces T cell mobilization and durable T cell responses in metastatic diseases. Here we present the ImmTAC platform and discuss our preclinical approach and progress with IMCgp100.

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Michael-Bethune
2:35 Discovery of Prostate Cancer-Reactive T Cell Receptors (TCR) for TCR Gene Therapy

Michael Bethune, Ph.D., Postdoctoral Fellow, Laboratory of David Baltimore, Division of Biology and Biological Engineering, Caltech

T cell receptor (TCR) gene therapy requires carefully selected antigenic targets and cognate TCRs. New platforms for target discovery and TCR isolation will facilitate expansion of this promising therapy to a broader array of cancers. This presentation will describe a novel platform for cloning tumor-reactive TCRs from tumor-infiltrating lymphocytes and identifying their antigenic targets through molecular display. Focus will be on prostate cancer, but the approach is general.

3:05 Presentation to be Announced


3:35 Refreshment Break


TUMOR INFILTRATING LYMPHOCYTES 

4:05 Talk Title to be Announced

Chantale-BernatachezChantale Bernatchez, Ph.D., Assistant Professor, Melanoma Medical Oncology, MD Anderson


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Adrian-Briggs
4:35 Identification of Anti-Cancer Antibodies and Antigens by Massively Parallel Sequencing of Tumor Infiltrating Lymphocytes

Adrian W. Briggs, Ph.D., Director, Molecular Biology R&D, AbVitro

Natural immune responses to cancer may hold the key to finding novel therapeutic targets. Our next generation immune sequencing platform recovers natively paired receptor genes from tumor infiltrating lymphocytes at unprecedented resolution. Using this technology we have isolated patient antibodies that strongly and selectively bind cancer tissue and kill cancer cells when presented as an antibody-drug conjugate. Work is underway to identify their target antigens.

5:05 End of Day

5:00 Dinner Short Course Registration*

Day 1 | Day 2 | Download Brochure | Speaker Biographies
UD: Unpublished Data | CS: Case Study 

FRIDAY, AUGUST 28

8:00 am Morning Coffee


PERSONALIZED IMMUNOTHERAPY APPROACHES 

8:25 Chairperson’s Opening Remarks

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

8:30 PANEL: Characterizing T Cell Therapies in the Clinic

  • Mechanistics aspects of adoptive cell therapy
  • On-treatment and predictive immunotherapy biomarkers
  • Relationships between clinical and immunological response

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

Panelists: Chantale Bernatchez, Ph.D., Assistant Professor, Melanoma Medical Oncology, MD Anderson

Julien Valton, Ph.D., R&D Project Leader, Cellectis

Luise U. Weigand, Ph.D., Team Leader, Cell Biology, Immunocore Ltd.

UD_Icon
Harpreet-Singh
9:00 FEATURED PRESENTATION: Personalized Cellular Immunotherapy against Novel Cancer Targets

Harpreet Singh, Ph.D., CSO and Managing Director, immatics biotechnologies GmbH


UD_Icon
Kipp_Weiskopf
9:30 Engaging Macrophages as Effectors of Cancer Immunotherapy

Kipp A. Weiskopf, Ph.D., Research Scientist, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine

Macrophages are innate immune cells that possess immense potential as effectors of cancer immunotherapy. Their ability to attack cancer can be unleashed by disrupting the CD47-SIRPa interaction, which acts as a myeloid-specific immune checkpoint. CD47-blocking therapies synergize with monoclonal antibody therapies, and their combination could yield personalized immunotherapeutic regimens that could be tailored to individual patients or tumor subtypes.

10:00 Coffee Break

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Harjeet Singh
10:30 Engineering T Cells for One and All

Harjeet Singh, Ph.D., Research Investigator, Pediatrics, MD Anderson Cancer Center

The administration of genetically modified T cells is championed by academia and industry alike. T cells are precision tools and one challenge now is to render them suitable for broad appeal as immunology is translated into immunotherapy. To help democratize T-cell therapy, I will reveal strategies how immune cells can be engineered ex vivo using a transposon/transposase system for in vivo applications. I will discuss how this non-viral approach to gene therapy can be combined immunotherapy to redirect specificity and improve the effector functions of T cells manufactured for clinical trials. For example, T cells can be genetically modified to express chimeric antigen receptors (CARs) to redirect specificity for cell-surface tumor-associated protein antigens and carbohydrates on fungi. I will reveal how the Sleeping Beauty (SB) system can be adapted and used to stably express CARs and TCRs to improve the therapeutic potential of clinical grade T cells. These clinical data serve as a foundation for additional genetic engineering to co-express transgenes to improve persistence as well as provide the opportunity for genome editing to eliminate undesired endogenous genes to improve T-cell potency and broaden their distribution and application.

11:00 Developing Potent Cancer Therapies Targeting Cancer Germline and Mutated Antigens

Paul-RobbinsPaul F. Robbins, Ph.D., Staff Scientist, Surgery Branch, Center for Cancer Research, National Cancer Institute

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.

11:30 Close of Target Discovery for T Cell Therapy



Day 1 | Day 2 | Download Brochure | Speaker Biographies 

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