CAR Ts, TCRs and TILs

Cambridge Healthtech Institute’s 7th Annual CAR Ts, TCRs and TILs focuses on the latest tools, techniques, and engineering strategies driving the development of cellular immunotherapies for cancer and immune disorders. Focus will be given to clinical progress with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), Tumor Infiltrating Lymphocytes (TIL) and Natural Killer (NK) cells, with dedicated sessions on off-the-shelf platforms, solid tumors and lessons learnt from the clinic.

Wednesday, September 2

CAR T INDUSTRY OVERVIEW

9:00 am

Industry Overview: Maximizing the Potential of T Cell Therapy Based on Lessons Learned in Clinical Studies and the Real World


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

CAR TS IN THE CLINIC

9:05 am KEYNOTE PRESENTATION:

Development, Clinical Results and Translational Analysis of CAR T Cell Products for Non-Hodgkin’s Lymphomas

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

Axi-cel and Brexu-cel, anti-CD19 CAR T cell products for lymphoma, have been approved to date for treatment of r/r DLBCL patients post third line therapy, and r/r patients with MCL, respectively. These products are heavily investigated and developed for treatment of other forms of malignancies. Two major questions have been whether this treatment modality can afford durable responses and potential cures in a subset of DLBCL patients, and whether similar clinical efficacy can be recapitulated in other B cell malignancies. In addition to summarizing key development steps and translational findings to date, we will showcase novel data speaking to the efficacy and toxicities of Axi-cel in DLBCL and iNHL, and of Brexu-cel in Mantle cell lymphoma patients.

TARGETING SOLID TUMORS

9:25 am

Engineering CARs for Solid Tumors

Paul Neeson, PhD, Associate Professor, Cancer Immunoloy Research, Peter MacCallum Cancer Centre

Solid tumor responses to CAR T cell therapy have been disappointing to date. To address this issue, we developed a new second generation CAR comprising a truncated human CD34, a scFV directed to Lewis Y, and endodomains CD28-CD3zeta in T cells that were enriched for 'early' T cells (stem cell and central memory-like). These "early" CAR T had enhanced proliferation, generating diverse progeny with increased cytotoxic function increased cytokine/chemokine secretion, and better in vivo therapy responses.

Rogier Reijmers, PhD, Principal Scientist, Immuno Oncology Department, LUMICKS

The overall binding strength (avidity) between cells is a crucial parameter for developing new immune cell therapies. An important obstacle is the lack of a fast and accurate technology to assess cellular binding avidity. The z-Movi® is a novel and unique instrument for direct measurement of cell–cell binding avidity using acoustic forces. We demonstrate that binding avidity of CAR and TCR transgenic T cells to tumor cells strongly correlates with in vitro functionality.

10:10 am

LIVE Q&A: Session Wrap-up

Panel Moderator:
Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad
Panelists:
Adrian Bot, PhD, Vice President, Translational Medicine, Kite Pharma, a Gilead Company
Paul Neeson, PhD, Associate Professor, Cancer Immunoloy Research, Peter MacCallum Cancer Centre
Rogier Reijmers, PhD, Principal Scientist, Immuno Oncology Department, LUMICKS
10:30 am Speed Networking Coffee Break - View our Virtual Exhibit Hall

TARGETING SOLID TUMORS

10:55 am KEYNOTE PRESENTATION:

Progress in Solid Tumors: CAR T Therapy in Mesothelioma

Prasad Adusumilli, MD, FACS, FCCP, Deputy Chief and Associate Attending, Thoracic Surgery; Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center; Associate Professor, Cardiothoracic Surgery, Weill Cornell Medical Center

Malignant pleural disease (MPD) from primary malignant pleural mesothelioma (MPM) or secondary metastatic disease (lung and breast cancers) affects more than 150,000 patients a year in the US alone. We developed chimeric antigen receptors (CARs) to target mesothelin (MSLN), a cell-surface antigen that we have shown is highly expressed in MPD, is associated with aggressiveness and poor survival, and has low expression in normal tissues.

11:15 am

Enhancing CAR T cell therapy by enabling CAR T cell interaction with antigen-presenting cells (APCs)

Clare Y. Slaney, PhD, Senior Research Officer, Peter MacCallum Cancer Centre

We generated novel bispecific proteins to mediate the interaction between APCs and CAR T cells. We termed these bispecifics “Bispecific Engagers of APCs and T cells (BEATs)”. CAR T cell proliferation and function was significantly enhanced by BEATs in the presence of APCs in vitro and in vivo. Importantly, murine syngeneic and human xenograft solid tumor growth was significantly inhibited when CAR T cells were administered in combination with BEATs.


Stephanie Scherer, Principle R&D Scientist, Advanced Genetic and Cell Technologies / Cell Design Studio, MilliporeSigma

Gene editing experts within MilliporeSigma’s Cell Design Studio™ provide custom cell line engineering services to create and deliver unique cell-based assays tailored for drug discovery and preclinical manufacturing. Our cellular models have been used for applications such evaluating efficacy of CAR-T cells, screening candidate checkpoint inhibitors, and generating potency assays for therapeutic testing. In this presentation, we will discuss the technology of these lines, their utility in immuno-oncology and novel therapeutic testing.

12:00 pm

LIVE Q&A: Session Wrap-up

Panel Moderator:
Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad
Panelists:
Prasad Adusumilli, MD, FACS, FCCP, Deputy Chief and Associate Attending, Thoracic Surgery; Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center; Associate Professor, Cardiothoracic Surgery, Weill Cornell Medical Center
Clare Y. Slaney, PhD, Senior Research Officer, Peter MacCallum Cancer Centre
Stephanie Scherer, Principle R&D Scientist, Advanced Genetic and Cell Technologies / Cell Design Studio, MilliporeSigma
12:20 pm Lunch Break - View our Virtual Exhibit Hall

ENGINEERING ALLOGENEIC CAR T CELLs

12:45 pm

Engineering of Allogeneic CAR T cells

Tom Van Blarcom, PhD, Senior Director, Head of Protein Engineering, Allogene Therapeutics

Allogeneic CAR T cells have shown encouraging preliminary Phase I clinical data demonstrating the potential promise of this therapy for more patients. This talk will highlight the critical areas that need to be addressed to maximize the dissemination of allogeneic CAR T cells and our approach to engineer optimal CARs that specifically targets tumors across a range of hematological malignancies and solid tumors.

1:05 pm

Engineering Gene-Edited Off-the-Shelf CAR T Cells to Reduce Immunogenicity and Improve Activity

Daniel T. MacLeod, PhD, Senior Director, Cell Therapy Discovery, Precision BioSciences

Gene editing can be used to generate off-the-shelf allogeneic CAR T cell products and to impart desirable features to improve their function. For our next generation of therapeutics, we are exploring gene knockout and incorporation of RNAi cassettes to modulate gene expression, with the goal of avoiding rejection, reducing T cell exhaustion, and enhancing function in the suppressive tumor microenvironment.

Julia Gilden, Sr Research Scientist, Integrated Biology, Research & Development, Promega Corporation

This presentation will discuss new bioluminescent tools to expedite the development of T cell-redirecting cancer therapies. First, we will describe two NanoBiT-based assay platforms that can quantitatively measure the potency of CD3 bispecific antibodies or BiTEs to induce T cell-dependent target cell killing and cytokine production. Next, we will describe TCRαβ-null reporter cell lines that can be used to screen transgenic TCRs against specific tumor antigen targets.

1:50 pm

LIVE Q&A: Session Wrap-up

Panel Moderator:
Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad
Panelists:
Daniel T. MacLeod, PhD, Senior Director, Cell Therapy Discovery, Precision BioSciences
Tom Van Blarcom, PhD, Senior Director, Head of Protein Engineering, Allogene Therapeutics
Julia Gilden, Sr Research Scientist, Integrated Biology, Research & Development, Promega Corporation
2:10 pm Refresh Break - View our Virtual Exhibit Hall

ENGINEERING ALLOGENEIC CAR T CELLs

2:25 pm

Gene Edited Off-the-Shelf Immunotherapies

Laurent Poirot, PhD, Vice President, Immunology, Cellectis

CAR T cells have proven successful in B cell malignancies but the unmet needs are still high in oncology. TALEN-mediated gene editing is highly efficacious, precise and specific. We are leveraging our expertise in gene editing to tailor properties of CAR T cells towards increasing their potency, rendering them resistant to tumor microenvironment while maintaining safety.

2:45 pm

Non-Gene Edited Allogeneic CAR T Cells: Maximizing Safety and Persistence

Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad

Targeting of CD3ζ by shRNA leads to efficient knockdown of the TCR complex, inhibiting GvHD in vivo and, importantly, allowing for increased persistence of T cells. Celyad’s “plug & play” shRNA allogeneic platform will be presented. Implementation of a T cell inhibitory peptide in the NKG2D CAR vector (CYAD-101) leads to blunting TCR activity and preventing GvHD. Clinical testing of CYAD-101 showed no significant toxicity and no GvHD. Clinical results will be presented.

3:05 pm

Session Wrap-Up

Panel Moderator:
Adrian Bot, PhD, Vice President, Translational Medicine, Kite Pharma, a Gilead Company
Panelists:
Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad
Laurent Poirot, PhD, Vice President, Immunology, Cellectis
Prem Mohanty, Product Marketing Manager, Marketing, Benchling
3:25 pm Session Break
3:50 pm Refresh Break - View Our Virtual Exhibit Hall
4:10 pm Problem Solving Breakout Discussions - Part A

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

TABLE 18: Mirror, Mirror on the Wall, Who Is the Finest CAR T Phenotype of Them All?

Peggy Sotiropoulou, PhD, Head, Research & Development, Celyad
  • What is the ideal memory phenotype for CAR T cells?
  • Is the ideal memory phenotype the same for autologous and allogeneic CAR T cells?
  • Does CD4/CD8 ratio matter?
  • Does the optimal CD4/CD8 ratio depend on the cancer type (heme vs. solid – hot vs. cold) and therapy type (autologous vs. allogeneic)?
4:40 pm Refresh Break - View Our Virtual Exhibit Hall
5:00 pm Problem Solving Breakout Discussions - Part B

TABLE 19: Present and Future of Genetically Engineered T Cells in Oncology

Adrian Bot, PhD, Vice President, Translational Medicine, Kite Pharma, a Gilead Company
  • Current results and limitations of CAR T therapy
  • Innovative receptor designs
  • Desired features of T cells: potency and controllability
  • Manufacturing optimizations to scale out, diminish cost, and fully utilize this platform technology
  • Beyond blood cancers and beyond cancer: what is next?
5:30 pm Close of Day

Thursday, September 3

ADVANCES IN TCRs AND TILs

9:05 am

CAR T: Mechanisms and Novel Therapeutic Strategies

Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, University of Pennsylvania

This presentation will provide an overview of the mechanisms of resistance to CAR T immunotherapy and strategies to develop rationally designed, next-generation immunotherapies.

9:25 am

TCR-Engaging Strategies to Eliminate Tumor Cells

Rajkumar Ganesan, PhD, Director, Antibody Engineering, Bispecifics and CAR T, Janssen

Redirecting the cytotoxicity of T cells by CD3-bispecific antibodies has resulted in remarkable clinical activity, albeit often accompanied by immune-related adverse events. IRAE is due to robust activation of T cells via CD3 rapid signaling, leading to severe cytokine storm that limits the dose of the drug, resulting in a narrow therapeutic index. To mitigate, a plethora of TCR-engaging strategies, such as modulating the affinity and epitope, are being explored.

9:45 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Adrian Bot, PhD, Vice President, Translational Medicine, Kite Pharma, a Gilead Company
Panelists:
Rajkumar Ganesan, PhD, Director, Antibody Engineering, Bispecifics and CAR T, Janssen
Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, University of Pennsylvania
10:30 am Coffee Break - View our Virtual Exhibit Hall

ADVANCES IN TILs

10:50 am

Advancements in Tumor-Infiltrating Lymphocytes in Treatment of Solid Tumors

Cecile Chartier, PhD, VP, Research, Iovance Biotherapeutics

Tumor infiltrating lymphocyte (TIL) therapy uses a patient’s own immune cells to attack cancer. Iovance is currently conducting pivotal studies in patients with metastatic melanoma and advanced cervical cancer. In addition, the company’s TIL therapies are being investigated for the treatment of patients with locally advanced, recurrent or metastatic cancers including head and neck and non-small cell lung cancer. Clinical studies of T cell therapy for blood cancers called peripheral blood lymphocyte (PBL) therapy are being planned.

11:10 am

Tumor-Infiltrating Lymphocytes Therapy for Solid Tumors

Chantale 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.

11:30 am

Session Wrap-Up

Panel Moderator:
Adrian Bot, PhD, Vice President, Translational Medicine, Kite Pharma, a Gilead Company
Panelists:
Cecile Chartier, PhD, VP, Research, Iovance Biotherapeutics
Chantale Bernatchez, PhD, Assistant Professor, Department of Melanoma Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
11:50 am Close of CAR Ts, TCRs and TILs





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