Enhanced central memory cluster of differentiation 8+ and tumor antigen-specific T cells in prostate cancer patients receiving repeated in situ adenovirus-mediated suicide gene therapy.

Abstract

The high relapse rate of prostate cancer following radical prostatectomy is clinically problematic, and various neoadjuvant therapies aimed at reducing the rate have been examined. A previous study has shown that immune responses are increased in patients treated by adenoviral vector-mediated herpes simplex virus-thymidine kinase (HSV-tk) gene delivery followed by ganciclovir (GCV) injection. However, details of the immune responses following this form of gene therapy remain unclear. Five patients who agreed to participate in the present phase I/II trial were repeatedly administered GCV intravenously for 2 weeks following intraprostatic injection of HSV-tk. Peripheral blood samples were periodically collected following the treatments, and lymphocyte subsets were analyzed by flow-cytometry. Intracellular interferon (IFN)-γ produced by T cells was further measured in response to prostatic acid phosphatase and NY-ESO-1 overlapping peptides. Central memory (CM) cluster of differentiation 8+ (CD8+) T cells were found to increase markedly during the second round of treatment. In three patients, tumor antigen-specific T cells were clearly increased following HSV-tk + GCV treatment. An increase in prostate cancer antigen-specific T cells and CM CD8+ T cells may contribute to a reduction of relapse rates in prostate cancer patients receiving this form of gene therapy, which shows promise in a neoadjuvant setting.