Brian Ruffel, PhD, Postdoctoral Scholar, Department of Cell & Developmental Biology
U.S. Bank Cancer Research Development Award
Title: "Targeting Immunosuppressive pathways to improve efficacy of adoptive cell transfer therapy"
Abstract: Cytotoxic T lymphocytes (CTLs) hold great potential as curative agents due to their ability to directly and selectively kill cancer cells. Though there are several hypothetical approaches to utilizing the potential of CTLs, the most effective clinical approach currently involves removal and expansion of tumor reactive CTLs, prior to readministration of the cells to patients in a process known as adoptive cell transfer (ACT). Commonly employed in the treatment of melanoma, ACT is especially potent when a portion of a patient's immune cells has already been depleted with chemotherapy or whole body irradiation, although an effective response is still not observed in a majority of patients. Despite these issues, ACT is currently being investigated for the treatment of breast cancer in early phase clinical trials. Using a recently generated mouse model system for examining ACT in breast cancer, we therefore plan to examine whether the optimal approaches identified for ACT in melanoma are transferable to the treatment of breast cancer. Furthermore, based upon recent findings that modulation of the immune system can improve response to therapy, we will investigate whether immune modulation can improve ACT, with the goal of reducing the requirement for pretreating patients with toxic therapies prior to ACT. These studies therefore hold potential for both informing ongoing clinical trials and improving patient care.