Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo (Publication with Expression of Concern. See vol. 14, 2019)

Aims: The aim of this study was to investigate the antimetastatic effect of multiple antigenic polypeptide (MAP) vaccine based on B-cell epitopes of heparanase (HPSE) on human hepatocellular carcinoma (HCC) in vivo. Methods: The antiserum against B-cell epitopes of HPSE was isolated, purified and characterized after immunizing white-hair-black-eye (WHBY) rabbit with freshly synthesized MAP vaccine. Tumor-bearing murine models of orthotopic implants using HCC-97H cell line were built in BALB/c nude mice. Anti-MAP polyclonal antibodies induced by MAP vaccine were administrated to the models. The impact on metastasis was assessed, the expressions of VEGF/bFGF in hepatoma tissues and in murine sera were evaluated, and the micro-vessel density (MVD) was counted as well. In addition, the possible impairments of the HPSE MAP vaccine on certain HPSE positive normal organs and blood cells were investigated. Results: The antiserum was harvested, purified and identified. The antibodies induced by MAP vaccine could specifically react with the dominant epitopes of both precursor protein and large subunit monomer of HPSE, markedly decrease HPSE activity, suppress the expressions of both VEGF and bFGF, and reduce the MVD. Pulmonary metastasis was also attenuated significantly by the anti-MAP polyclonal antibodies. In addition, no obvious impairment could be observed in certain HPSE positive organs and cells. Conclusion: MAP vaccine based on B-cell epitopes of HPSE is capable of alleviating HCC metastasis in vivo, mainly through inhibiting the HPSE activity and tumor associated angiogenesis, by virtue of the specific anti-MAP polyclonal antibodies. Furthermore, these HPSE-specific antibodies do not cause obvious abnormalities on certain HPSE positive blood cells and organs. Our study provides theoretical evidences for the clinical use of the synthesized MAP vaccine based on B-cell epitopes of HPSE in preventing HCC metastasis.