CAR Ts, TCRs and TILs

 

Novel gene editing technologies and a greater understanding of cancer biology could unleash the full power of CAR T in both blood and solid tumors. But which therapies will succeed?

Cambridge Healthtech Institute’s Sixth Annual CAR Ts, TCRs and TILs conference focuses on the latest research, protein engineering and clinical strategies driving the development of adoptive cell therapies across a wide range of indications. Clinical progress with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), Tumor Infiltrating Lymphocytes (TIL), and NK cells will be addressed as well as new strategies for commercialization will be reviewed.

Final Agenda

TUESDAY, APRIL 9

Recommended Short Course*

SC10: CAR T-Cell Therapy for Solid Tumors

Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School

 

Moonsoo M. Jin, PhD, Professor, Biomedical Engineering, Radiology & Surgery, Molecular Imaging Innovations Institute, Weill Cornell Medical College

Tara Arvedson, PhD, Director, Oncology Research, Amgen

 

*Separate registration required.

WEDNESDAY, APRIL 10

7:15 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)

7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided) (Waterfront 1&2)

Moderator:

Jennifer-ChadwickJennifer S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-Chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter


Panelists:

Joanna BrewerJoanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune


Charlotte A. RussellCharlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience


Susan RichardsSusan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D


Kristi SarnoKristi Sarno, Senior Director, Business Development, Pfenex


CAR T MECHANISMS, RESISTANCE AND NOVEL TARGETS
waterfront 1&2

8:30 Chairperson’s Opening Remarks

Bob Valamehr, PhD, Chief Development Officer, Fate Therapeutics


8:40 KEYNOTE PRESENTATION: Mechanisms of CAR Treatment Success and Failure Based on Clinical Experience in Lymphoma and Leukemia

Bot AdrianAdrian Bot, PhD, Vice President, Translational Sciences, Kite Pharma, a Gilead Company

As CAR T cell therapy is now standard of care in certain B cell malignancies, novel data point to mechanistic aspects related to treatment success or failure, essential to advance next-generation therapies. In this presentation, we cover factors influencing clinical outcomes: product T cell fitness, integrating the number and polyfunctionality of specialized T cell subsets, tumor burden and immune microenvironment, and biological aspects intrinsic to the cancerous process.

9:10 Resistance to CART19 Therapy: Mechanisms and Novel Therapeutic Strategies

Ruella_MarcoMarco Ruella, MD, Clinical Instructor, Associate Director, Dr. June’s Laboratory, Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania

Chimeric Antigen Receptor T cell (CAR T) have generated impressive clinical results for CD19+ B cell leukemia and lymphoma. However, a significant subset of patients still does not respond or eventually relapses. I will discuss the mechanisms of resistance to CART19 and present future developments.

9:40 Novel Targets and Technologies for CAR T Cells in Multiple Myeloma and Acute Myeloid Leukemia

Mestermann_KatrinKatrin Mestermann, PhD, Post-Doc, Max Eder Research Group‚ CAR T-Cell Engineering, Department of Medicine II, University Hospital Würzburg

Translational research in CAR T cell immunotherapy involves a rapidly increasing portfolio of novel target antigens, CAR designs, and technologies to enhance safety, efficacy and physician control. This talk will review the latest developments from our program including novel targets in hematology and oncology, and novel technologies for high-throughput screening, ultra-fast manufacturing, and real-time control over CAR T cells after administration in vivo.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

10:15 Women in Science Speed Networking in the Exhibit Hall (Commonwealth Hall)

10:55 Targeting TCR-β Constant Domain for Immunotherapy of T Cell Malignancies

Ferrari_MahieuMatthieu Ferrari, PhD, Senior Scientist, Protein Engineering, Autolus

Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. We report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 (TRBC1 and TRBC2). Unlike nonselective approaches targeting the entire T cell population, TRBC-targeted immunotherapy could eradicate a T cell malignancy while preserving sufficient normal T cells to maintain cellular immunity.

OFF-THE-SHELF CAR Ts
waterfront 1&2

11:25 FEATURED PRESENTATION: Allogeneic CAR T: The Next Revolution in Cell Therapy

Sasu_BarbraBarbra Sasu, PhD, CSO, Allogene

While allogeneic CAR T research is at an earlier stage, encouraging Phase 1 clinical data demonstrates the promise of this therapy for more patients. The talk will highlight the clinical data available to date and the overall research strategy to develop a pipeline of allogeneic CAR T therapies across a range of hematological and solid tumor indications.

11:55 Gene Edited Off-the-Shelf Immunotherapies

Andre Choulika, PhD., Chairman and CEO, Cellectis

A limitation of the current autologous approach is that CAR T-cells must be manufactured on a "per patient basis". Cellectis has developed a platform for generating chimeric antigen receptor (CAR)-redirected T-cells from third-party healthy donors using transcription activator-like effector nucleases (TALEN®). Nuclease mediated inactivation of the TCR alpha abrogates the potential for T-cells bearing alloreactive TCR's to mediate Graft versus Host Disease (GvHD). Additional gene inactivation events can be incorporated, permitting resistance to lymphodepleting or chemotherapeutic agents, resistance to tumor inhibition or suppression of cross T-cell reactions. Such allogeneic “off-the-shelf” CAR T-cell products will permit a wider application of CAR technology and potentially lead to a new paradigm in cancer treatment.

Isoplexis

12:25 The Functional Capacity of Immune Cells Predicts Clinical Outcome Across IO Therapies

Singleterry_WillWill Singleterry, PhD, Director, Business Development, IsoPlexis

Using single cell proteomics to measure the functional capacity or ‘fitness’ of immune cells has correlated with and been predictive of clinical outcome in CAR-T, TIL, Cancer Vaccine and Checkpoint Inhibitor therapy.  This talk will review several of these data sets and discuss applications of IsoPlexis’ single cell technology.

Oxford-Genetics 12:40 Mammalian Display Antibody Discovery for Integral Membrane Proteins

Ryan Cawood, PhD, Oxford Genetics

Through co-expression of integral membrane targets and scFv molecule libraries in a mammalian cells we show that cells that exhibit self-labelling can be purified and lead molecules identified via NGS analysis. Lead candidates are then suitable for either CAR-T or antibody reformatting.

 

12:55 Luncheon Presentation I: Genetically Modified Cell Lines for Immuno-Oncology Cell-Based Assay Development

Ward_StacyStacy Ward, PhD, Senior Research & Development Scientist, Cell Design Studio, MilliporeSigma12:55

MilliporeSigma’s Cell Design Studio™ cell line engineering service offering is the premier research partner for generating customized cell-based assays and immunotherapy research models. Our team has generated new monoallelic HLA panel expression cell lines and tumor-associated antigen panels, which express individual tumor antigens at varying levels in biologically-relevant cell lines. In this presentation, we will discuss the breadth of these lines and discuss their utility in immuno-oncology and therapeutic testing.

1:25 Luncheon Presentation II (Sponsorship Opportunity Available)

1:55 Session Break

OFF-THE-SHELF CAR Ts (CONT.)
waterfront 1&2

2:10 Chairperson

Adrian Bot, PhD, Vice President, Translational Sciences, Kite Pharma, a Gilead Company

2:15 Rejection-Resistant T Cell Platform for an Off-the-Shelf Therapy

Mamonkin_MaxMaksim Mamonkin, PhD, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine

‘Off-the-shelf’ (OTS) T cell products pre-manufactured from healthy donors are readily available and less costly than autologous products, offering similar therapeutic potency. However, immune rejection by host T- and NK-cells may limit the persistence of OTS cells and compromise their anti-tumor activity. We engineered alloimmune defense receptors (ADRs) that enable OTS T cells to recognize and eliminate alloreactive lymphocytes resulting in complete protection from immune rejection while retaining full functionality.

2:45 Translation of Pluripotent Cell-Derived T and NK Cells as a Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Valamehr_BobBob Valamehr, PhD, Chief Development Officer, Fate Therapeutics

Pluripotent cell technology represents a powerful approach to make cell-based immunotherapies available to a wide range of patients through the generation of a consistent and renewable “off-the-shelf” source of cellular therapeutics. I will discuss our progress towards developing unique and effective strategies to create a renewable source of genetically engineered “off-the-shelf” T and NK cells with augmented function. Updates on IND filings and FIH progress will also be given.

3:15 Epitope Identification and Clinical Immune Monitoring in Gene Therapy and Immune Oncology Programs

Knowlton_EmileeEmilee Knowlton, PhD, Immunology, Sales Specialist, Sales, ProImmune, Inc.

Epitope discovery is a crucial element in the development of vaccine candidates and drug therapeutics. In the Immune-oncology space, identifying neoepitopes and tumor-associated antigens provide new targets for cancer diagnostics and enable the tracking of patient responses to treatment. ProImmune provides industry-leading tools for antigen characterization, epitope mapping and immune monitoring. In this presentation, case studies will be shared that detail how ProImmune’s integrated platform has identified novel epitopes in the immune-oncology field.

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

4:45 Problem-Solving Breakout Discussions - Click here for details (Commonwealth Hall)

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

7:00 End of Day

THURSDAY, APRIL 11

8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)

CAR NK CELLS, TCRs AND TILs
waterfront 1&2

8:30 Chairperson’s Remarks

Adrian Bot, PhD, Vice President, Translational Sciences, Kite Pharma, a Gilead Company

8:35 Combining Innate and Adaptive Immunity: NK Receptors for CAR T Cell Therapy

Bornschein_SimonSimon Bornschein, PhD, Scientist, Celyad

The success of CAR T therapy against B-cell malignancies generated high expectations for all cancers, but the target remains the challenge. NKG2D binds to 8 different ligands present on a broad range of tumors yet largely absent on healthy tissue indicating a potential breadth of applicability of the approach. Our approache to exploring the therapeutic power of NKG2D CAR T cells in the autologous (CYAD-01) and allogeneic (CYAD-101) setting will be discussed.

9:05 Gene Editing of Stem Cells for Universal SPEAR T-Cell Therapy

Brewer_JoJoanna Brewer, PhD, Vice President, Platform Sciences, AdaptImmune

Adoptive T cell therapy using autologous material for CAR and TCR therapies show considerable promise. However, an off-the-shelf product will speed up the time to treat patients and provide a consistent and unlimited source of therapeutic cells. Stem cells are also amenable to genetic modification, allowing them to remain hidden from the immune system for long-term persistence of differentiated T cells expressing enhanced affinity TCRs.

9:35 Organize, Optimize, and Measure Biologics R&D with Modern Software

Bhimji_AlyaAlya Bhimji, PhD, Field Applications Scientist, Benchling

Benchling is a biologics-native informatics platform used by over 160,000 scientists to configure biologics workflows and run day-to-day R&D. This presentation will highlight how Benchling has helped leading biopharma companies to organize, optimize, and measure their biologics R&D.

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

11:05 ImmTAC™: Engineering Soluble Bispecific TCRs, with High Specificity and Affinity, to Treat Cancer

Vijaykumar Karuppiah, PhD., Senior Scientist, Immunore

11:15 Immatics' Discovery and Validation Platform for Tumor-Specific T Cell Receptors

Sara Yousef, PhD., Research Scientist, Immatics

11:25 Functional TCR-T Cell Screening Using Single-Cell Droplet Microfluidics

Weian Zhao, PhD., Associate Professor, Department of Pharmaceutical Sciences, University of California, Irvine

11:35 Tumor Infiltrating Lymphocytes Therapy for Solid Tumors

Bernatchez_ChantaleChantale Bernatchez, PhD, Assistant Professor, Department of Melanoma Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

In TIL therapy T cells are grown from solid tumor samples and expanded to large numbers ex vivo to be infused back to the patient. The therapy has been very successful in metastatic melanoma with a 42% clinical response rate at our institution and others with most of the responses being durable. Despite great results we are at this point investigating why the other half of the patients would not respond. Through molecular and immunological assays we are trying to define biomarkers that could predict response to therapy. Another focus of our research is to test the efficacy of TIL therapy in other solid tumor types.

12:05 pm Advancements in Tumor Infiltrating Lymphocytes in Treatment of Solid Tumors

DiTrapani_KellyKelly DiTrapani, VP, Medical Affairs, Iovance Biotherapeutics

Iovance is developing TIL, a one-time cell therapy treatment that leverages and enhances the body’s natural defenses against certain solid tumors. TIL is being investigated in several multi-center Phase 2 clinical trials and preliminary results have demonstrated safety and efficacy in melanoma, head and neck and cervical cancer patients. While available immunotherapies for solid tumors, such as anti-PD-1 antibodies have shown promise, additional agents are needed for patients who may progress on such therapies or are intolerant.

12:35 End of CAR Ts, TCRs and TILs

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