Immunotherapy of Prostate Cancer with Genetically Enhanced Tumor- Specific T Cell Precursors

摘要

Adaptive immunity can contribute significantly to tumor immunosurveillance and anti-tumor activity of cancer treatment regimens. We have reported previously that in vitro generated T cell precursors can be adoptively transferred across MHC barriers to allogeneic hosts and demonstrated that genetically engineered tumor-specific T cell precursors mediate enhanced anti-tumor responses. In this project we have proposed to generate genetically engineered prostate cancer-specific T cell precursors and test their efficacy for tumor immunotherapy in mouse models of prostate cancer. We now report that we have established non-myeloablative regimens to support engraftment of T cell precursors and established a prostate cancer model to test our adoptive therapy strategy. Non-myeloablative regimens were developed using a combination of radiation limited to the thymic region and cytoxan chemotherapy. The prostate cancer model (both localized and disseminated) was established using inoculation of RM1 cell line expressing human prostate specific membrane antigen (PSMA). We also report that we have optimized the transduction of T cell precursors with chimeric antigen receptor (CAR) targeting PSMA- pZ1.