Design,preparation,and antitumor activity of fusion protein vaccine based on tumor antigen PBK
PBK is a cancer/testis antigen that exhibits absent expression in various normal human tissues,but undergoes aberrant overexpression upon cellular transformation,thereby promoting the initiation,metastasis and even drug resistance of cancer.Consequently,it represents a novel target for tumor immunotherapy.In this study,PBK-Nitrath,a protein vaccine specifically designed to target PBK by fusing nitrated T epitope with the PBK protein was developed,using the IFN-γ ELISpot method to evaluate the activation level of PBK antigen-specific T cells in the spleen of immunized mice,and conducting in vitro cytotoxicity T cell killing efficacy test to evaluate the killing ability against H22 hepatic carcinoma cells;the anti-tumor activity was evaluated using a H22 hepatic carcinoma subcutaneous transplantation tumor model,and the differentiation of peripheral blood and spleen T lymphocytes and tumor immune infiltration were analyzed by flow cytometry.Results showed that PBK-Nitrath could efficiently induce the activation of antigen-specific T cells against PBK while enhancing cytotoxic T lymphocyte-mediated killing capacity,significantly impede hepatic carcinoma progression in mice and increase the ratio of CD8+CD107a+T cells within peripheral blood and spleen,and facilitate tumor lymphocyte infiltration.Our findings reveal the potential utility of PBK-Nitrath as an effective candidate for tumor vaccine.