Cell Manipulation Core
The Cell Manipulation Core Facility (CMCF) produces safe and effective cellular components, including hematopoietic progenitor cells, tumor and dendritic cell vaccines, and other cellular immunotherapy products. All procedures are performed by highly trained personnel according to current Good Manufacturing Practices (cGMPs) for cell and tissue processing.
In collaboration with the Center for Human Cell Therapy, the core has begun to develop a series of new manufacturing procedures to support highly innovative new cell-based therapies. One of these new studies focuses on the ex vivo expansion of invariant Natural Killer T (iNKT) cells for adoptive therapy in patients with cancer. Steven Balk, MD, PhD (BIDMC), F. Stephen Hodi, MD (DFCI), and colleagues at the Cancer Vaccine Center have initiated a phase I clinical trial which evaluates the feasibility and safety of generating purified and ex vivo expanded autologous iNKT cells in patients with advanced melanoma. In this study, patients first undergo leukopheresis and a monoclonal antibody specific for the human iNKT receptor linked to biotin-conjugated magnetic beads is used to purify patient iNKT cells. Autologous iNKT cells are enriched using CliniMACS, a magnetic cell sorting device manufactured by Miltenyi, and expanded in tissue culture media containing human AB serum, OKT-3 and IL-2 over 6-8 weeks. After sufficient numbers of cells are obtained, the expanded iNKT population is cryopreserved. Subsequently three equal doses of iNKT cells are thawed and infused on days 1, 15, and 29. This clinical trial is supported by the Cancer Vaccine Center and represents the first human study of adoptive therapy with expanded iNKT cells. The immunologic effects of iNKT cell infusion are monitored closely as well as potential toxicities of infusing large numbers of in vitro expanded cells.
The Cell Manipulation Core has successfully purified and expanded iNKT cells for the first 4 patients enrolled on this study. Three patients have received all 3 infusions of expanded iNKT cells without significant toxicity. The fourth patient in the study has recently begun to receive iNKT cell infusions and will also receive GM-CSF to further modulate iNKT cell activity in vivo. The study is ongoing and further development of this novel approach will depend on the clinical and immunologic effects of treatment that are observed as these patients are carefully monitored.
