Specific antitumor immune response induced by a novel DNA vaccine composed of multiple CTL and T helper cell epitopes of prostate cancer associated antigens

Abstract

The loss of immunogenic epitopes by tumors has urged the development of vaccines against multiple epitopes. Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. In this study, several DNA fragments encoding multiple cytotoxic T lymphocyte (CTL) and T helper (Th) cell epitopes were selected from human prostate-specific membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human prostate-specific antigen (hPSA), These DNA fragments were ligated together to form a novel fusion gene, termed 3P gene. The 3P gene and human IgG Fc gene were inserted into pcDNA3.1 to construct a DNA vaccine designated psig-3P-Fc. Vaccination with psig-3P-Fc by gene gun inoculation induced strong antitumor response in a mouse tumor model, which significantly inhibited tumor growth and prolonged survival time of the tumor-bearing mice. In vitro, when lymphocytes were stimulated by psig-3P-Fc-transfected autologous peripheral blood mononuclear cells (PBMC), CTLs were induced which could specifically kill hPSM-, hPAP-, or hPSA-expressing tumor cells. These observations provide a new vaccine strategy for cancer therapy through concomitant enhancement of antigen specific CD4 + helper and CD8 + cytotoxic T-cell responses against tumors.