Preparation for a Clinical Trial Using Adoptive Transfer of Tumor- Reactive TGF-Beta-Insensitive CD8+ T Cells for Treatment of Prostate Cancer

摘要

Prostate cancer is the most common form of malignancy and is the second leading cause of cancer mortality in American men. While the medical field is able to treat locally confined prostate cancer, metastatic diseases remain to be a major medical challenge. Treatment of advanced stage tumors usually requires a systemic approach. However, conventional therapeutic approaches are only palliative at best. Therefore, new approaches are urgently needed for patients with advanced metastatic prostate cancer. The present proposal describes a novel immunotherapy program based on our understanding of the action of TGFbeta. Results of our pre-clinical studies have demonstrated that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells to hosts bearing mouse prostate tumors resulted in a complete rejection of established tumors. We observed that these CD8+ T cells were able to infiltrate into the tumor parenchyma, secrete relevant cytokines, and mediate apoptosis in tumor cells. These observations are encouraging. We propose to quickly translate this technology into a clinical setting for the treatment of patients with advanced prostate cancer. In the present application, we propose to perform all preparations so that all requirements for a clinical trial will be in place.