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Recent advances in protein engineering and molecular biology have increased the feasibility of using genetically engineered T cells to treat disease, leading to an influx of new discoveries and techniques. With these new 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 second annual Adoptive T Cell Therapy will review the latest strategies for target discovery, as well as T cell receptors (TCRs), chimeric antigen receptors (CAR), and tumor infiltrating lymphocytes (TILs) against tumor antigens. This event will focus on issues facing the field with an emphasis on engineered T cells and the use of adoptive T cell transfer to facilitate therapeutic treatments for cancer, infectious diseases, and bone marrow transplants. Clinical data will be showcased, as well as in depth examinations of where the field is headed.

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WEDNESDAY, MAY 6

7:00 am Registration and Morning Coffee

CAR, TCR, and TIL  

8:00 Chairperson’s Remarks

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

8:10 CAR T Cell Therapy; The CD19 Paradigm and Beyond

Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center

T cell engineering provides a powerful means to rapidly generate large supplies of tumor-targeted T cells for cancer immunotherapy. CARs are recombinant receptors that retarget and reprogram T cell function to destroy tumor cells, sustain T cell persistence and enhance T cell function within the tumor microenvironment. The CD19 model has emerged as the paradigm for CAR therapy, paving the way for tackling other cancers.

8:40 Affinity-Enhanced TCRs for Adoptive T Cell Therapy

Gwendolyn K. Binder-Scholl, Ph.D., Executive Vice President & Head, Clinical and Regulatory Affairs, Adaptimmune, LLC

This talk will review the rationale for, and the method of, production and preclinical screening methodology applied to generate affinity enhanced T cell receptors. Recent clinical data from studies of autologous T cells modified with affinity enhanced T cell receptors (TCRs) specific to NY-ESO-1 will be presented, as well as plans for future targets/TCRs.

9:10 Clinical Development of Tumor-Infiltrating Lymphocyte Therapy for Solid Tumors: The Myths and the Reality

Laszlo G. Radvanyi, Ph.D., Chief Scientific Officer, Lion Biotechnologies

Many of the patients treated with TILs have progressed after multiple therapies, including checkpoint blockade with anti-CTLA-4 and anti-PD-1/PD-L1, making TIL also an ultimate salvage therapy option. In this presentation, we will discuss common misconceptions about TIL therapy and current efforts that can realistically bring TIL therapy into the mainstream as an approved product for melanoma care as well as its promise as a cellular therapy for other solid cancers.

9:40 PANEL DISCUSSION: CAR vs. TCR vs. TIL

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

Panelists: Laszlo G. Radvanyi, Ph.D., Chief Scientific Officer, Lion Biotechnologies

Gwendolyn K. Binder-Scholl, Ph.D., Executive Vice President & Head, Clinical and Regulatory Affairs, Adaptimmune, LLC

Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory; Stephen and Barbara Friedman Chair, Memorial Sloan-Kettering Cancer Center

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

PREDICTING AND PREVENTING TOXICITY 

11:25 Ensuring the Safety of Cellular Therapy

Unpublished DataMalcolm K. Brenner, MB, Ph.D., Founding Director, Professor, Center for Cell and Gene Therapy, Baylor College of Medicine

Unlike toxicities from small molecule therapeutics, cell therapies may cause harm that persists and worsens over time. Genetic modification of transplanted cells to incorporate a suicide or safety system that can be activated as required should ameliorate this problem. We developed an inducible caspase 9 molecule that can kill cells with the desired properties of speed, effectiveness and titratability and will describe its clinical application.

11:55 Clinical Manufacturing of Chimeric Antigen Receptor (CAR) T Cells Targeted to Carcinoembryonic Antigen (CEA)

Pranay Khare, Ph.D., Director, Cancer Immunotherapy and Gene Therapy cGMP Facility, Roger Williams Medical Center

We recently completed phase I Hepatic Immunotherapy for Metastases (HITM) trial with CEA targeted CAR-T cells. We tested the safety of CEA specific CAR-T cells by hepatic artery infusions (HAI) for unresectable CEA+ liver metastases (LM). We successfully produced and infused 18 doses of CEA CAR-T cells under good manufacturing practice (GMP) facility. The safety of CEA targeted CAR-T cells and further advancement in the CAR-T cell production process will be discussed.

12:25 pm Sponsored Presentation (Opportunity Available)

12:55 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:55 Session Break

PREDICTING AND PREVENTING TOXICITY CONT. 

2:10 Chairperson’s Remarks

Michelle Krogsgaard, Ph.D., Assistant Professor, New York University Perlmutter Cancer Center, New York University School of Medicine

2:15 Mechanisms of Efficacy and Acute Toxicity after Adoptive CAR T Cell Treatment

Charles Sentman, Ph.D., Professor, Microbiology & Immunology, Geisel School of Medicine

Chimeric antigen receptors based on NK cell receptors have shown efficacy in tumor models of lymphoma, ovarian cancer, and multiple myeloma. Extensive testing has been done to evaluate the mechanisms for how these CAR T cells interact with host cells and the tumor microenvironment. At very high cell doses, an acute toxicity response similar to cytokine release syndrome has been observed. Both the CAR T cell and host contribute to this toxicity through specific mechanisms. This presentation will describe the mechanisms involved in anti-tumor efficacy and acute toxicity after adoptive therapy with these CAR T cells.

2:45 In vivo Functionality of Immune Cells Engineered via Vector Free Intracellular Delivery

Armon Sharei, Ph.D., Founder, SQZ Biotech

In this presentation we describe a novel method for the ex vivo delivery of materials directly to the cytoplasm of primary immune cells and the subsequent minimal effect on immunological function of the adoptively transferred cells. To demonstrate the immunological capabilities of the engineered cells, protein antigen was delivered to antigen presenting cells and the in vivo T cell activation was measured. In a murine model we show that compared to incubation with the antigen, intracellular delivery causes a 10-100x increase in antigen specific T-cell proliferation for a robust immune response.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

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THURSDAY, MAY 7

8:00 am Morning Coffee

TARGET DISCOVERY AND ANTIGEN SELECTION 

8:30 Chairperson’s Remarks

Armon Sharei, Ph.D., Founder, SQZ Biotech

8:35 Novel Cancer Targets for Adoptive Cellular Therapy

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

9:05 Durable Clinical Responses without Persisting CAR T Cells in Circulation or Protracted On-Target Toxicity

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

It is believed that long lasting CAR-T cells are a prerequisite for durable clinical responses, leading to protracted on-target off-tumor toxicities in cases of targets shared by normal tissues. Based on this paradigm, some efforts have been directed mainly at optimizing CAR technologies for CAR-T cell persistence in peripheral blood as a surrogate biomarker. However, the largest clinical efficacy data set in aggressive and indolent lymphomas has been generated with CD19-targeting CAR-T cells of a CD28zeta configuration.

9:35 Translating Adoptive T Cell Therapies to Clinical & Commercial Reality

Usman Azam, M.D., Global Head Cell & Gene Therapies, Cell & Gene Therapies Unit, Novartis

Adoptive T cell therapies have flourished on the scientific front. The next frontier fast approaches – how to turn these promising platforms into clinical and commercial reality.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

ENHANCING EFFICACY OF IMMUNOTHERAPIES 

11:05 Engineering the Immune Response to “Self” for Effective Adoptive T Cell Therapy

Michelle Krogsgaard, Ph.D., Assistant Professor, New York University Perlmutter Cancer Center, New York University School of Medicine

We are taking a variety of biophysical and cellular imaging approaches to determine how specific thresholds for T cell recognition of self (tumor)-antigens are set. Our recent results indicate that antitumor activity and autoimmunity are coupled and have a similar kinetic threshold; reducing autoimmunity cannot be accomplished without sacrificing efficacy of tumor killing. New strategies to overcome this issue includes careful engineering of tumor-specific TCRs and T cell signaling pathways to carefully balance tumor-reactivity and autoimmunity.

11:35 Targeting Tumor-Induced Immunosuppression Leads to Potent Anti-Tumor Responses by CAR T Cells

Phil Darcy, Ph.D., Group Leader, Cancer Immunotherapy, Peter MacCallum Cancer Centre

A major problem inhibiting Adoptive Immunotherapy is the immunosuppressive mechanisms utilized by tumors to suppress immune clearance and thus facilitate tumor cell survival. One of these immunosuppressive pathways which has largely been ignored is the generation of adenosine by CD73 expressed on tumor cells. We demonstrated that blocking the A2A receptor with the small molecule antagonist SCH58621 could enhance the ability of chimeric antigen receptor (CAR) transduced T cells targeting the Her-2 antigen to produce cytokines and reject established tumors in vivo. This study shows that specifically blocking tumor induced immunosuppression can potently enhance CAR T-cell therapy and this has significant implications for potentially improving therapeutic outcomes of CAR T cell therapy for patients.

12:05 pm Sponsored Presentation (Opportunity Available)

12:35 End of Conference

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