Antitumor immunity of DNA vaccine based on CTLA-4 fused with HER2 against colon carcinoma

Abstract

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) negatively regulates the T cell activation and competes with CD28 in binding with B7.1/B7.2 molecules. Fusion of the extracellular region of CTLA-4 and a specific antigen is an effective method for improving the immune efficacy of DNA vaccines. This study aimed to investigate the effects of DNA vaccine of human epidermal growth factor receptor-2 (HER2) fused with CTLA-4 on the development of colon carcinoma in mice and to identify the potential immune mechanisms underlying its effects. We constructed recombinant plasmids corresponding to the control group, individual antigen group, and fusion antigen group. Then, mice were intramuscularly injected with the corresponding plasmids and exposed to electrical pulses. Immunogenicity was evaluated at 2 weeks after the last immunization. Furthermore, to investigate the antitumor immune effects of the recombinant plasmid, we established a mouse model of HER2 expression in transplanted tumors. Experimental results showed that the recombinant plasmids expressing fusion antigen induced a stronger cellular immune response. Inoculation of the HER2-CTLA-4 plasmid exerted the strongest inhibitory effect on HER2 expression-mediated tumor growth in mice. These results highlight the potential of the CTLA-4 fusion DNA vaccine as a therapeutic vaccine against colon cancer based on HER2 and CTLA-4.