Human Cancer Immunology
Human T cell immunity to melanoma is the chief interest of our research laboratory. Two projects are ongoing with the primary goal of developing proof of principle clinical trials using new cell therapy approaches at Washington University School of Medicine/Siteman Cancer Center. We collaborate and work closely with other clinical melanoma experts as well as basic scientists and utilize molecular and cell biology techniques. Rapid translation from the research laboratory to the clinic is emphasized. Clinical-grade autologous cell products are manufactured at the Siteman Biologic Therapy Core GMP facility located on the medical center campus.
Functionally mature IL-12 producing Dendritic Cells (DC) administered as a vaccine can elicit type-1 polarized, antigen-specific CD8+ T cells in patients with advanced melanoma. Of the patients treated on this study (JCI 2013), 3 patients exhibit objective confirmed clinical responses and 2 patients remain alive and well after 5 years. Our data suggests that the vaccine-primed Tc1 polarized T cells have replicative potential and remain highly avid in the recognition of naturally processed antigen presented on autologous tumor cells. We have begun a new clinical trial to identify and target tumor-specific unique antigens.
Vaccine-primed T cells can be expanded in vitro using a new synthetic MHC construct identified in our laboratory (J Immunology 2012). We are exploring the use of vaccine-primed autologous T cells for adoptive therapy in order to test new hypotheses related to the melanoma tumor microenvironment. Emphasis is placed on studying the functional traits of peripheral blood and tumor-infiltrating T cells in trial participants.
A related interest is participation in industry-sponsored and cooperative group clinical trials for patients with melanoma. Our interests include signal transduction inhibitors as well as new immunotherapy agents, including gene transfer approaches with viral vectors. The long-term goal is to develop effective personalized immunotherapy for patients with melanoma.