The overarching goal of our research is to develop cellular immunotherapy into a treatment modality for patients with cancer and to foster this goal through translational, developmental, basic and applied basic research in immunology. In general, the research focus in our lab can be divided into clinical studies, translational/developmental studies and basic studies in T cell immunity. Since 1995, our lab has been developing strategies to isolate and expand tumor‐associated antigen-specific T cells for treating patients with solid tumor malignancies and to identify the intrinsic and extrinsic factors influencing T cell survival, function and efficacy. To ensure that we would be able to more precisely evaluate the reasons for success or failure of a given approach, we postulated that a well‐defined population of T cell clones of uniform specificity, phenotype and magnitude would be instrumental in addressing immunologic questions and provide a highly functional anti‐tumor effector population for adoptive therapy. To this end, a series of first-in-human clinical trials using antigen-specific T cell clones was designed to evaluate the influence of various lymphodepletion regimens on the in vivo persistence and function of transferred T cells, the contribution of antigen-specific CD8 and CD4 T cell clones to the anti-tumor effect and the potential for combined modality approaches that include the use of immune checkpoint inhibitors and post-infusion vaccination to mediate a durable anti-tumor response. It has become apparent from the work of others in the field and our own studies that the intrinsic properties of the T cell, in particular its replicative capacity and potential to persist as memory cells can influence its anti‐tumor efficacy. We postulate that strategies to enrich for a highly replicative tumor-antigen-specific T cell population will be instrumental in establishing T cell memory in vivo and durable clincial responses. While our initial studies focused on the treatment of melanoma, we have begun to evaluate the feasibility of treating patients with other solid tumor malignancies such as ovarian cancer and sarcoma. Ultimately, we believe that a combined modalities approach incorporating vaccination, adoptive cellular therapy and manipulation of the tumor immune environment will be required for effective anti-tumor response and lifelong memory. We have been fortunate to receive support from the NIH and also several nonprofit foundations without whose support many of the most innovative studies could not have been accomplished or even attempted: Cancer Research Institute, Damon Runyon Cancer Research Foundation, Edson Foundation, and the Burroughs Wellcome Fund. We are also indebted to the many patients on our clinical trials who inspire us with their courage and generosity.
Fred Hutchinson Cancer Research Center (Primary)
University of Washington School of Medicine (Secondary)