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The Islet Product, Planning for Trials, and Manufacturing

Tuesday April 25, 2023 - 10:15 to 11:30

Room: Riverfront

S7

.3 Planning for clinical trials: Lessons learned from autologous iPSC-derived products

Jerome Ritz, United States

Executive Director, Connell and O'Reilly Families Cell Manipulation Core Facility
Medical Oncology
Dana-Farber Cancer Institute

Biography

Dr. Ritz is currently Professor of Medicine in the Department of Medical Oncology at the Dana-Farber Cancer Institute, Brigham and Woman’s Hospital and Harvard Medical School. His research laboratory focuses on the assessment of donor immune function after allogeneic hematopoietic stem cell transplantation (HSCT) and characterization of immune mechanisms responsible for graft versus leukemia (GVL) and graft versus host disease (GVHD). These laboratory studies have led to new clinical approaches to enhance GVL and prevent or treat GVHD. His lab also studies other cellular therapies for hematologic malignancies including CAR-T cells and activated NK cells. Working closely with clinical collaborators he has developed approaches to precisely characterize the effects of these treatments on immune function in vivo. These results are correlated with clinical outcomes such as response and toxicity to develop a better understanding of the immunologic mechanisms that contribute to these outcomes. Dr. Ritz is also the Executive Director of the Connell and O’Reilly Families Cell Manipulation Core Facility at the Dana-Farber Cancer Institute (DFCI). This GMP cell manufacturing facility supports both adult and pediatric hematopoietic stem cell transplant programs at DFCI, Brigham and Women’s Hospital and Boston Children’s Hospital and also provides a variety of novel cellular products for patients enrolled on clinical trials at DFCI and Harvard-affiliated hospitals. This facility recently expanded to include 15 cleanrooms available to manufacture a variety of cellular products including genetically modified hematopoietic stem cells, genetically modified immune cells (CAR T cells), regulatory T cells, natural killer cells, induced pluripotent stem cells (iPSC) and other complex cellular products. This facility is a critical resource for both academic investigators and industry sponsors interested in developing innovative cellular therapies.

Abstract

Planning for clinical trials: manufacturing autologous iPSC-derived products

Jerome Ritz1,2.

1Dana-Farber Cancer Institute, Boston, MA, United States; 2Harvard Medical School, Boston, MA, United States

Generation of iPSC-derived cellular products for clinical use is now clearly feasible and transplantation of allogeneic stem cell-derived islet cells has shown promising results. Creating large batches of allogeneic cells for potential use in many patients has clear advantages from a manufacturing perspective. However, there are also limitations to this approach since allogeneic tissues are susceptible to immune rejection in the recipient requiring long-term immune suppression or other experimental approaches to maintain graft function. Generation of cellular products from autologous iPSC avoids graft rejection due to histo-incompatibility but generation of iPSC from individual patients and subsequent differentiation of small batches of autologous products is currently very labor intensive and time consuming. Despite these limitations, generation of autologous iPSC-derived products is feasible for small numbers of patients and clinical trials are ongoing. However, process improvements and automation will be required to make this approach practical for clinical evaluation in large numbers of patients.


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