Role of cell surface GM3 ganglioside and sialic acid in the antitumor activity of a GM3-based vaccine in the murine B16 melanoma model.
OBJECTIVE
To examine the role of GM3 monosialoganglioside and sialic acid in the antitumor activity of a vaccine based on GM3, hydrophobically conjugated with the outer-membrane-protein complex from Neisseria meningitidis (GM3/VSSP).


METHODS
In order to evaluate the relationship between antitumor activity and the presence of GM3 on the surface of tumor cells, we used two murine tumor cell lines with different ganglioside expression. Syngeneic mice were immunized with four i.m. doses of GM3/VSSP (120 micro g) at 14-day intervals and challenged subcutaneously with tumor cells.


RESULTS
B16 melanoma cells showed GM3 on cell surface and GM3-dependent in vitro growth. As expected, preimmunization with the vaccine significantly inhibited tumor formation and prolonged survival in mice challenged with B16 cells. In contrast, no antitumor effect was observed in mice challenged with GM3-negative F3II mammary carcinoma cells. The reactivity of sera from immunized mice against B16 cells was confirmed by flow cytometry and immunoperoxidase staining. Depletion of sialic acid residues from the cell surface completely abolished antibody response against melanoma cells.


CONCLUSIONS
These results indicate that the antitumor activity of GM3/VSSP is associated with GM3 expression on tumor cell surface and demonstrate a major role of sialic acid in the humoral response of vaccinated mice.
Gabri
Mariano R
MR
Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Bernal B1876BXD, Buenos Aires, Argentina. mrgabri@unq.edu.ar
Ripoll
Giselle V
GV
Alonso
Daniel F
DF
Gómez
Daniel E
DE
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005679:G(M3) Ganglioside / Q000276:immunology* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019158:N-Acetylneuraminic Acid