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.

Final Agenda

Day 1 | Day 2

TUESDAY, MAY 5

Recommended Short Course*

SC10: CAR T Cell Therapy from A-Z

*Separate registration required.

WEDNESDAY, MAY 6

7:15 am Registration and Morning Coffee

7:25 Women in Science Panel Discussion with Continental Breakfast

Moderator: Lucie Rochard, PhD, Liaison, Scientific & Entrepreneurial Initiatives; Director, Innovation Services, Massachusetts Biotechnology Council

CLINICAL UPDATES AND TARGETING SOLID TUMORS

8:40 Chairperson’s Opening Remarks

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

8:50 KEYNOTE PRESENTATION: Development, Clinical Results and Translational Analysis of CAR T Cell Products For Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma

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

Axi-cel, a first in class anti-CD19 CAR T cell product for lymphoma, has been approved to date for treatment of r/r DLBCL patients post third line therapy. The same CAR molecule is 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 tumor types. 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 at 3 years follow up, and of a similar product in Mantle cell lymphoma patients post BTKi treatment failure.

9:20 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.

9:50 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.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Women in Science Speed Networking in the Exhibit Hall

11:05 Engineering the “CAR” of Allogeneic CAR T Cells

Tom Van Blarcom, PhD, Head, 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.

11:35 Engineering Gene-Edited Off-the-Shelf CAR T Cells to Reduce Immunogenicity and Improve Activity

Daniel 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.

12:05 pm Translation of Pluripotent Cell-Derived T and NK Cells for Off-the-Shelf Cancer Immunotherapy

Bob Valamehr, PhD, Chief Development Officer, Fate Therapeutics

Several obstacles currently hamper the broad use of adoptive cell therapies, including the absolute requirement for precise genetic editing of multiple elements, the elimination of undesired stochastic events associated with cellular engineering and the inherent variability and cost of manufacturing. Here we present a unique approach to create a master pluripotent stem cell line, clonally derived to contain precisely edited events selected at the single cell-level and the continuous conversion of that master cell line into uniform populations of highly efficacious off-the-shelf engineered CAR T and NK cells.

12:35 Sponsored Presentation (Opportunity Available)

1:05 Session Break

1:10 LUNCHEON PRESENTATION I: Genetically-Engineered Immuno-Oncology Cell Lines and Services for Early Drug Discovery

Suzanne Hibbs, MS, MBA, Senior Product Manager, Cell Design Studio, MilliporeSigma

MilliporeSigma’s Cell Design Studio™ gene-editing experts provide premier custom cell line engineering services to create/deliver unique cell-based assays tailored for drug discovery and preclinical manufacturing. Our cellular models have been used in evaluating efficacy of CAR-T cells, screening candidate checkpoint inhibitors, and generating potency assays for therapeutic testing. We’ve also generated new functional biologically-relevant tumor-associated antigen and monoallelic HLA panel cell lines that express either individual tumor antigens at varying levels or individual HLAs.

1:40 Luncheon Presentation II (Sponsorship Opportunity Available)

2:10 Session Break

ALLOGENEIC T CELL THERAPY

2:25 Chairperson’s Remarks

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

2:30 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.

3:00 Non-Gene Edited Allogeneic CAR T Cells: Maximizing Safety and Persistence

Peggy Sotiropoulou, PhD, Director, 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.

3:30 Presentation to be Announced

3:45 Presentation to be Announced

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Problem-Solving Breakout Discussions

6:00 Taste of New England Networking Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day

Day 1 | Day 2

THURSDAY, MAY 7

8:00 am Registration and Morning Coffee

ADVANCES IN TCRs AND TILs

8:30 Chairperson’s Remarks

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

8:35 A Novel TCR Engineering Approach 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 (IRAEs). Prime reason for 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 engineering strategies such as modulating the affinity and epitope are being explored.

9:05 Clinical Experience with T Cells Expressing NY-ESO-1 TCR and CRISPR Edited to Eliminate Endogenous TCR and PD-1

Simon Lacey, PhD, Director, Translational and Correlative Studies Laboratory, Center for Cellular Immunotherapies, University of Pennsylvania

NY-ESO-1 is a cancer testis antigen with aberrant expression in myelomas, sarcomas, and melanomas. I will present updated data from a Phase I pilot clinical trial for patients with advanced MM and sarcoma of T cells expressing a TCR recognizing a HLA-A201 restricted NY-ESO-1/LAGE-1 157-165 epitope (SLLMWITQC) and with CRISPR/Cas9 TCRα, TCRβ and PDCD1 edited genes (NCT03399448).

9:35 Sponsored Presentation (Opportunity Available)

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

11:05 New Broadly Expressed Cancer Targets from Successful TIL Therapy

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumour-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant tumour-reactive T cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted T cell targets that are expressed by many other tumour types.

11:35 Advancements in Tumor Infiltrating Lymphocytes in Treatment of Solid Tumors

Corrine Epperly, MD, MPH, Senior Vice President, Strategy and Operations, 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.

12:05 pm 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.

12:35 End of CAR Ts, TCR and TILs

Recommended Short Course*

SC14: USP Standards to Support Quality of Potency Measurements

*Separate registration required.

Day 1 | Day 2

* The program is subject to change without notice, due to unforeseen reason.