The fusion protein of HSP65 with tandem repeats of β-hCG acting as a potent tumor vaccine in suppressing hepatocarcinoma

Abstract

It has been demonstrated that the β-subunit of human chorionic gonadotropin (β-hCG) is ectopically expressed on a variety of human cancers of different histological types and has been used as an antigenic target in anti-cancer vaccines. We engineered a fusion protein by fusing 10 tandemly repeated copies of the 10-residue sequence of β-hCG (109–118) (in CTP37) combined with β-hCG C-terminal 37 peptides to mycobacterial heat-shock protein 65 and immunized mice via subcutaneous injection. Humoral immune and cellular immune responses were effectively elicited. High titer of anti-β-hCG antibody was detected in immunized mice sera by ELISA and verified by Western blot analyses. The fusion protein of HSP65-X10-β-hCGCTP37 effectively inhibited the growth of tumor both protective and therapeutic anti-tumor immunity in hepatocellular carcinoma tumor models in mice. Meanwhile, it also attenuated tumor-induced angiogenesis in intradermal tumor model in mice. Taken together, these results demonstrate that immune responses are effectively induced by a novel fusion protein vaccine targeting β-hCG, suppressing the growth of hepatocellular carcinoma in mice. The β-hCG-targeted vaccine holds promise for the treatment of a number of cancers and merits further study.