Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Abstract

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.

Immunotherapy of prostate cancer using novel synthetic DNA vaccines targeting multiple tumor antigens

“…Notably, PSCA is considered as an effective marker for late stage PCa as its overexpression possess strong correlation with advancing tumor grade, stage, and progression to androgen independence [ 37 ]. In addition, it anchors to cancer cell surface without exocytosis and therefore it is considered as a highly suitable target antigen for PCa immunotherapy [ 38 ]. PSP94, also known as prostatic inhibin or β-micro semino protein is one of the most abundant proteins in semen along with PSA and PAP.…”

Evaluation of the preventive and therapeutic effects of a recombinant vector co‐expressing prostate‐specific stem cell antigen and Clostridium perfringens enterotoxin on prostate cancer in rats

“…They showed that this PSCA‐based vaccine can induce long‐term protection against PCa development in PCa‐prone transgenic adenocarcinoma mouse prostate mice and reported that vaccination induced MHC Class I expression and cytokine production (IFN‐γ, tumor necrosis factor‐A, interleukin 2 [IL‐2], IL‐4, and IL‐5) within prostate tumors. In the other study, Mai et al constructed a fusion plasmid containing the PSCA gene and cytotoxic T‐lymphocyte associated antigen‐4 (CTLA‐4) and evaluated its antitumor effect in an animal model of PCa. Their study showed mice immunized with pVAX1‐PSCA‐F2A‐CTLA‐4 exhibited greatly increased secretion of the Th1 (IFN‐g) and Th2 cytokines (IL‐4).…”