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.
WEDNESDAY, MAY 6
7:00 am Registration and Morning Coffee
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 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.
9:10 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
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
11:25 Ensuring the Safety of Cellular Therapy
Malcolm 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., Consultant
12:25 pm Enjoy Lunch on Your Own
1:55 Session Break
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., CEO, 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 Safely yet Effectively Harnessing the Immuno-Oncology Target: CD47
Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA
Harnessing the intrinsic anti-tumorigenic power of immune cells has shifted the paradigm for treating cancer patients. While T cell targeting methodologies are evolving to widen the risk/benefit window, a future parallel approach will
be to incite other lineages, such as macrophages, to participate in efficacy. Our strategy is to use a bi-specific antibody format to elicit tumor specific phagocytosis. In several preclinical settings, combining the ‘right’
potency of an anti-CD47 arm with a high affinity arm for a tumor associated antigen (e.g., CD19, mesothelin) afforded specific macrophage-mediated tumor killing in a safe yet effective manner. Preparations for entering clinical trials
are ongoing.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
Adoptive T Cell Therapy for Tumors
Pranay Khare, Ph.D., Consultant
- Development of Chimeric Antigen Receptors (CARs)
- Modification and expansion of T cells with CARs
- T cell receptor (TCR) and Armed T cell
- Achievements and Challenges of adoptive T cell therapy
Combination Therapies for Cell Therapy
Moderator: Laszlo G. Radvanyi, Ph.D., Chief Scientific Officer, Lion Biotechnologies
- Low hanging fruit: What therapy combinations are available now to augment adoptive T-cell therapy
- Roadblocks to testing combination therapies with T cells
- There are so many possible combination therapies targeting many pathways in cancer and the immune system to combine with cell therapy
- How do we prioritize these trials?
- How do we de-risk the system and minimize failure?
- Role of biomarker studies and identifying biomarkers in T cells therapy to identify new combination therapy targets
- Does one size fit all? How would combo therapies for CART, TCR-transduced cells, and TIL be similar or different?
5:45 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
THURSDAY, MAY 7
8:00 am Morning Coffee
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
Current targeted adoptive cell therapy approaches that have reached the clinic are mostly directed against cell surface-resident proteins (through CAR-T cell approaches) and a handful of established target structures. Going after particularly
solid cancers will require a larger and more diverse repertoire of targets. TCR-T cell approaches allow targeting all cellular antigens including intracellular ones. Here we present how the powerful combination of ultra-high sensitivity
mass spectrometry, next-generation sequencing, T-cell immunology and bioinformatics (aka the XPRESIDENT® platform) allows discovery, selection and preclinical validation of novel antigens and T-cell receptors suitable for the next
wave of adoptive cell therapies.
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 such as CD19. 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, emerging clinical evidence especially in aggressive and indolent lymphomas, challenges
the paradigm that long lasting CAR T cells accompanied by on target toxicity, are needed for durable clinical responses.
9:35 Rational Development and Characterization of Chimeric Antigen Receptors For New or Difficult Targets
Marcela Maus, Ph.D., M.D., Assistant Professor, Medicine, Perelman School of Medicine; Director, Translational Medicine and Early Clinical Development, Translational Research Program, Abramson Cancer Center, University of PennsylvaniaWe will review the kinds of characterization that are performed in vitro and in vivo in bringing a new CAR T cell product to the clinic. We will discuss targeting mutant surface proteins on tumor cells, with particular attention to EGFR variant III.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
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 LATE BREAKING PRESENTATION: NanomAbs: A Novel Targeted Nanomedicine Platform for Improved Cancer Therapy
Zahra Shahrokh, Ph.D., Chief Development Officer, STC Biologics
12:35 End of Conference