Antitumor Protection by NGcGM3/VSSP Vaccine Against Transfected B16 Mouse Melanona Cells Overexpressing N-Glycolylated gangliosides

Abstract

Background: Cancer vaccines are designed to modulate immunological responses against tumor cells through the presentation of tumor antigens. Materials and Methods: The mouse mRNA of the cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah) gene, the enzyme that catalyzes the synthesis of N-glycolylneuraminic acid (NGc), was cloned and transfected into the B16 melanoma cell line. Transfected cells (B16-H) were characterized and used as an NGcGM3-positive primary tumor model for the evaluation of the therapeutic activity of the NGcGM3/VSSP vaccine. Results: The presence of NGcGM3 in B16-H cells promoted proliferation and adhesion in vitro, but resulted in reduced tumorigenicity in vivo. However, B16-H cells developed growing tumors in mice where NGcGM3/VSSP vaccination induced a therapeutic antitumor activity. NGcGM3/VSSP was ineffective in mice inoculated with parental B16 or B16-H cells that had lost NGcGM3 expression. Conclusion: The presence of NGcGM3 in tumor cells is critical for the antitumor activity of NGcGM3/VSSP vaccine.