Plenary Keynotes

1:15 Manufacturing Chimeric Antigen Receptor T Cells for Early Phase Clinical Trials

David F. Stroncek, M.D., Chief, Cell Therapy Section, Transfusion Medicine, NIH Clinical Center

The NIH Center for Cellular Engineering manufactures cell and gene therapy products for intramural campus clinical trials. The CCE has manufactured more than 150 Chimeric Antigen Receptor (CAR) T cells for several clinical trials over the past 5 years. All the CAR T cells have been manufactured from autologous cells which creates several manufacturing challenges. Many small lots of cells must be produced, each of which require special handling, in-process and lot release testing, and quality review. While many of these CAR T cell clinical trials have yielded promising clinical results, final product consistency has been problematic. All are CAR T cell products are manufactured using autologous peripheral blood mononuclear cells (PBMC) concentrates collected by apheresis. The composition of the PBMCs is highly variable due to the patients’ disease and prior treatments. We have found large quantities of monocytes and granulocytes in the PBMCs were associated with poor CAR T cell expansion. We have made several modifications in the T cell enrichment step which have improved cell yields but some of the changes in T cell enrichment may be effecting CAR T cell quality. In conclusion, the manufacturing of CAR T cells is challenging due to the logistical and testing issues associated with manufacturing autologous therapies and inconsistent cell expansion due to highly variable cellular starting material.

2:05 Evolution of Cancer Immunotherapy

Ramy Ibrahim, M.D., VP, Clinical Development, Parker Institute for Cancer Immunotherapy

Keynote Speaker Biographies

Ramy IbrahimRamy Ibrahim, M.D., VP, Clinical Development, Parker Institute for Cancer Immunotherapy

Ramy Ibrahim, MD, is a recognized leader of clinical development in immunotherapy. He helped develop some of the first breakthrough treatments in the field during his tenure at Bristol-Myers Squibb and MedImmune/AstraZeneca. Dr. Ibrahim currently serves as vice president of clinical development at the Parker Institute for Cancer Immunotherapy. At AstraZeneca, Dr. Ibrahim was the vice president of clinical development for Immuno-oncology, leading the team developing multiple immunotherapies. Molecules developed under his leadership included durvalumab (anti-PD-L1 antibody) and tremelimumab (anti-CTLA-4 antibody) both with single drug and combination therapies with a focus on registrational studies in multiple indications including lung cancer, bladder cancer and head and neck cancer. As a member of the Bristol-Myers Squibb Immuno-oncology program, he served on the Yervoy (ipilimumab) clinical team supporting the program from early phase II through multiple global launches of the first FDA-approved immune checkpoint inhibitor. In addition, he played a key role in early development for nivolumab (PD-1), PD-L1 and CD137 antibody. Throughout his career, Dr. Ibrahim has been involved with global cancer immunotherapy societies such as the Society of Immunotherapy for Cancer (SITC), Ludwig Institute, the Cancer Research Institute and Cancer Immunotherapy Trials Network (CITN). He is a trained medical oncologist, who conducted bench and clinical immunotherapy research at the cancer vaccine branch of the National Cancer Institute in Bethesda, MD.

David StroncekDavid F. Stroncek, M.D., Chief, Cell Therapy Section, Transfusion Medicine, NIH Clinical Center

A native of Minnesota, Dr. David Stroncek completed his undergraduate and medical school degrees, an internal medicine residency, and a hematology/oncology fellowship at the University of Minnesota. He then joined the faculty of the University of Minnesota Medical School, Laboratory Medicine and Pathology Department and later became medical director of the blood blank. He helped establish the National Marrow Donor Program (NMDP) and was the organization's first medical director. During his four years as medical director of the NMDP, the program coordinated their first unrelated donor transplant and subsequently increased the number of marrow donations by unrelated individuals. He has served on several NMDP committees as president of the council of the NMDP and as a member of the NMDP board of directors. Dr. Stroncek came to the NIH Clinical Center Department of Transfusion Medicine (DTM) in 1996 as chief of the Laboratory Service Section. In this role, he directed the HLA and Transfusion Services Laboratories. During his tenure, the HLA laboratory moved from a serological laboratory to a molecular testing laboratory that provided sequence-specific probe, high resolution sequence-specific primer, and sequence-based HLA genotyping. Under Dr. Stroncek's direction, the Transfusion Service Laboratory began genotyping RBC antigens and discovered that the low pH and high osmolarity of citrate anticoagulant in blood components caused RBCs from donors with sickle cell trait to occlude leukocyte reduction filters. Dr. Stroncek became chief of the Cell Processing Section in 2007. Under his direction the Section has collaborated with Institute Investigators to develop and implement methods to produce clinical Natural Killer cell, dendritic cell, bone marrow stromal cell, Chimeric antigen receptor (CAR) T cell and viral specific T cell products. He is also working on developing new cellular therapies, improving existing cellular therapies, investigating the mechanisms of action of cellular therapies, identifying potency markers and developing potency assays. He has published more than 294 articles in scientific journals and has written several book chapters. He has served on the editorial boards of several scientific journals.