Cambridge Healthtech Institute’s Third Annual

Adoptive T-Cell Therapy

Success from Bench to Bedside with Improved Approaches

19-20 March 2018 | Hilton London Canary Wharf | London

 

In Adoptive T Cell Therapy, investigators from academia and industry present a fascinating range of approaches focusing in particular on optimization of specificity together with avoidance of off-site toxicity. This track presents new developments for attacking solid tumours, the potential for non-personalized therapies, and efforts to automate and simplify the process. Data from bench to bedside including preclinical models, translational studies and successes in the clinic will be included.

 

Final Agenda

Monday, 19 March

08:00 Registration & Morning Coffee

NEXT GENERATION TECHNOLOGIES

09:00 Chairperson’s Opening Remarks

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

 

 

09:10 KEYNOTE: ImmTAC® Reagents: Novel Bi-Functional TCR-Based Biologics for Targeted Immunotherapy

Bent Jakobsen, PhD, CSO, Immunocore

We have developed novel, bi-functional soluble T cell receptor (TCR) ImmTAC® (Immune mobilising monoclonal TCR against Cancer) which consists of an affinity-enhanced TCR linked to an anti-CD3 effector domain. ImmTAC molecules bind specific peptides presented on the cell surface by human leukocyte antigen, vastly increasing the number of potential targets. Our lead ImmTAC molecule, IMCgp100, is currently undergoing clinical trials for the treatment of advanced cutaneous and uveal melanoma. Additional ImmTAC molecules are in development for a variety of other cancers.

09:40 Development of the Next Generation of Chimeric Antigen Receptors (CARs) for the Treatment of Solid Tumors

Richard Morgan, PhD, Vice President, Immunotherapy, bluebird bio

Genetically-engineered CAR T cells are designed to supplement a patient’s immune system and can be further engineered to survive and potentially to overcome immune evasion mechanisms employed by cancer cells. We found that addition of a PI3-kinase inhibitor during CAR T cell manufacture represented a facile method to enrich for memory-like CAR T cells. Combined with gene editing and synthetic biology, we hope to develop CAR T cell technology for use in the treatment of solid tumors.

10:10 Advances with Allogeneic Gene-Edited CAR-T Cells

Laurent Poirot, PhD, Head, Early Discovery, Innovation, Cellectis

T-cell adoptive immunotherapy emerges as a powerful approach in oncology. Cellectis technologies combined with 18 years of gene editing experience enable efficient and specific editing of any gene in primary cells and offer unparalleled possibilities for the next generation of immunotherapies. TALEN technology allows creation of non-alloreactive allogeneic CAR T-cells while also empowering cells with additional safety and efficacy attributes such as resistance to then tumour microenvironment and compatibility with standard of care.

10:40 Sponsored Presentation (Opportunity Available)

11:10 Networking Coffee Break

TUMOUR INFILTRATING LYMPHOCYTES AND UNCONVENTIONAL T CELLS

11:40 Next Generation Products Based on Tumour Infiltrating Lymphocytes

Robert Hawkins, MB BS, MRCP, PhD, FRCP, Cancer Research UK Professor, Medical Oncology, University of Manchester & Honorary Consultant, Medical Oncology, Christie Hospital

Tumour Infiltrating Lymphocytes (TIL) are a prognostic biomarker in many tumours and have therapeutic efficacy in many tumour types. They can be used in a variety of ways to evolve next generations products, e.g. to enhance efficacy and to improve survival and proliferation by introducing novel genes. TILs can provide a rich source of tumour specific TCRs which can be cloned for conventional TCR based gene therapy or TCR libraries to produce synthetic TIL.

12:10 The Advantages of Targeting Cancer with Unconventional T-Cells and T-Cell Receptors

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

The major subsets of human T-cells target processed protein antigens presented as peptides bound to HLA at the cell surface. Our dissection of successful cancer immunotherapy and other pipelines has identified various broadly tumoricidal T-cell clones that are not HLA-restricted. These unconventional T-cells can kill most cancer types from all patients and thereby offer hope for pan-population, pan-cancer diagnostics and therapeutics.

12:40 Sponsored Presentation (Opportunity Available)

13:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:40 Session Break

BENEFITS OF PREDICTIVE BIOMARKERS, CHARACTERIZATION, AND AFFINITY OPTIMISATION

14:00 Chairperson’s Remarks

Boris Engels, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis, Inc.

 

 

 

14:05 Advances in CAR-T Therapy for Chronic Lymphocytic Leukemia (CLL)

J. Joseph Melenhorst, PhD, Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

We have shown that CD19-specific chimeric antigen receptor (CAR) T cell therapy can induce durable remission in most patients with acute but not chronic lymphocytic leukemia (ALL and CLL). We have now identified markers predictive of response and identified key mechanisms of response in CLL. Our preclinical studies have informed next-generation CAR-T based therapies for CLL. Our current trial in CLL has trumped our highest expectations in terms of response rate.

14:35 Analytical Characterization Studies for CAR-T Cell Therapy

David G. Kugler, PhD, Senior Scientist, Team-Lead, T Cell Profiling, Juno Therapeutics, Inc.

Chimeric antigen receptor (CAR)-T cells are a promising new modality for cancer immunotherapy, and many variants are rapidly being developed across the immuno-oncology space for haematological and solid tumor malignancies. The field has displayed enormous promise; however, the rules governing which attributes drive efficacy are still being learned. Here, we present early insights from transcriptomic and epigenetic profiling of CAR-T cells describing how cell state may play an important role.

15:05 Taking TCR-Engineered Cells to the Clinic

Tom Holdich, MBBS, Head, Global Medical Affairs & EU Clinical Development, Clinical Research, Adaptimmune

Adoptive T-cell therapy is a novel approach to treatment that has demonstrated promising results but also presents unique challenges in development. Adaptimmune has developed Specific Peptide Engineered Antigen Receptor (SPEAR) T-cells with affinity-optimized TCRs that recognize intracellular cancer-expressed antigens. This requires target selection, TCR development, non-clinical safety testing and scalable manufacture. SPEAR T-cells targeting MAGE-A10, MAGE-A4, and AFP are in clinical trials in several solid tumor indications.

15:35 Networking Refreshment Break

INNOVATIVE APPROACHES

16:05 Small Molecule Control of CAR-T Cells

Simon Thomas, PhD, MBioch, Associate Director, Immunobiology, R&D, Autobus Ltd.

CAR-T cells are autonomous and after infusion they engraft and expand; hence, unlike small molecular or protein therapeutics, they have no half-life. Toxicity can therefore be progressive and fulminant. We have developed a number of different strategies for “remote control” of CAR-T cell activity whereby CAR-T cells are engineered to respond to small molecule drugs. These different approaches will be described and contrasted.

16:35 Synthetic Biology: Minimizing Toxicity and Maximizing Efficacy with Adoptive T Cell Therapies

Peter Emtage, PhD, CSO, R&D, Cell Design Labs

We have developed technologies that provide novel cellular control mechanisms to reduce toxicities while maximizing efficacy. The Throttle switch and synNotch technologies enable control of intrinsic activity of the CAR T with a definable mechanism in the case of Throttle switch and a logic gated decision paradigm in the case of synNotch. Application of these systems in the clinic enables modulation of safety issues like CRS and on/off target toxicities while maximizing efficacy.

17:05 Problem Solving Roundtable Breakout Discussions

18:00 Welcome Reception in the Exhibit Hall with Poster Viewing

19:00 End of Day

Tuesday, 20 March

ADVANCING ADOPTIVE T-CELL THERAPY IN THE CLINIC

08:00 Registration & Morning Coffee

08:30 Chairperson’s Remarks

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London

 

 

 

08:35 Advancing CAR-T Cell Therapy to the Clinic

Eric L. Smith, MD, PhD, Assistant Attending, Myeloma & Director, Clinical Translation, Cellular Therapeutics, Memorial Sloan Kettering Cancer Center

CAR-T cell therapy has proved to have dramatic efficacy in relapsed/refractory B-ALL. In addition to CD19 targeted CAR-T cell therapy (B-ALL, CLL, NHL), we have developed and translated to the clinic CAR-T cell therapy products targeting PSMA (Prostate), Mesothelin (Lung, Breast), MUC16 (Ovarian), and most recently BCMA (Myeloma). Furthermore, we developed and translated novel ‘armored’ CAR-T cell approaches including the co-expression of 4-1BBL (B-cell malignancies) or IL12 (Ovarian).

09:05 TCR-Engineered T Cells Combined with T Cell Co-Stimulation to Treat Solid Tumors

Reno Debets, PhD, Associate Professor, Tumor Immunology, Medical Oncology, Erasmus MC Cancer Institute

To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs and, at the same time, include strategies that restore or enhance accumulation and activation of T cells in tumor tissues. Here, we present our recent preclinical and translational studies to enhance TCR-engineered T cell therapy, its combination with T-cell co-stimulation, and preparations towards a clinical T cell therapy trial to treat patients with melanoma and head-and-neck cancer in 2018 Q2.

09:35 Design of a Highly Efficacious CAR Targeting Mesothelin in Solid Tumors

Boris Engels, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis, Inc.

Following clinical experience with a murine scFv based CAR (SS1) targeting mesothelin (MSLN), we pursued the generation of a fully human MSLN-targeting CAR with increased potency against solid tumors. The strong anti-tumor activity of the lead CAR was confirmed in a unique primary pancreatic cancer xenograft mouse “clinical trial”. The lead candidate is now being evaluated in a Phase I clinical study in patients with malignant mesothelioma, ovarian, and lung cancer.

10:05 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

ADVANCES IN THE CLINIC WITH SOLID TUMOURS

11:15 Challenges of Targeting Solid Tumours with CAR-T Cells in the Clinical Setting

Fiona Thistlethwaite, MB, PhD, Consultant, Medical Oncology, The Christie NHS Foundation Trust

For solid malignancies, significant hurdles still need to be overcome if CAR-T cell therapy is to become a valid strategy in the clinical setting. These challenges include the identification of appropriate tumour antigens that avoid on-target/off-tissue toxicities, achieving adequate T-cell homing, and overcoming the immune suppressive tumour micro-environment. These aspects will be discussed in the context of CEA targeted CAR-T cell therapy for solid malignancies.

11:45 ErbB Targeted CAR-T Cell Immunotherapy of Head and Neck Cancer: T4 Immunotherapy

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London

T4 immunotherapy consists of a CD28+CD3z-based chimeric antigen receptor (CAR), targeted against the extended ErbB network, and which is co-expressed with an IL-4 responsive chimeric cytokine receptor. Preclinical efficacy and safety has been demonstrated in models of head and neck, ovarian, breast cancer and mesothelioma. Phase I clinical evaluation is now ongoing in patients with locally advanced or recurrent head and neck cancer, employing intra-tumoural delivery to minimize toxicity.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Close of Adoptive T-Cell Therapy