A novel hydrophobized GM3 ganglioside/Neisseria meningitidis outer-membrane-protein complex vaccine induces tumor protection in B16 murine melanoma.
Gangliosides are sialic acid-containing glycosphingolipids that have increased surface membrane expression on cancers of neuroectodermal origin. The present study was designed to investigate at a preclinical level the therapeutic usefulness of a consistently immunogenic and safe conjugate vaccine in melanoma. We have examined a novel vaccine of GM3 monosialoganglioside hydrophobically conjugated with the outer-membrane-protein complex from Neisseria meningitidis plus Montanide ISA 51 in the B16 melanoma mouse model. B16 cell line is characterized by the predominant presence of ganglioside GM3 on the cell surface. Vaccines were administered i.m. in the quadriceps at 14-day intervals and B16 cells were injected in the subcutis of the right flank of C57BL/6 mice, 7 days after the fourth dose. Significant suppression of tumor growth and prolongation of survival were seen by immunization with GM3 vaccine in animals challenged with 5x10(3) or 10(3) live melanoma cells. In addition, vaccination reduced tumor growth in animals challenged with 5x10(4) cells. The reactivity of serum IgG from vaccinated mice was examined by a sensitive immunoperoxidase assay on B16 tumor specimens. Most melanoma cells displayed a distinct positive staining associated with both cell membrane and cytoplasm. In accordance with the immunohistochemical stainings, the antisera of immunized mice reacted brightly against B16 melanoma cells in flow cytometry studies. Anti-sera also mediated complement-mediated cytotoxicity and specific response could be totally ascribed to antibodies of the IgG2b subclass. The present data suggest that GM3 vaccine may provide a useful immunotherapeutic strategy for melanoma.
Alonso
D F
DF
Laboratorio de Oncologia Molecular, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes, Bernal, 1876 Buenos Aires, Argentina.
Gabri
M R
MR
Guthmann
M D
MD
Fainboim
L
L
Gomez
D E
DE
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D003167:Complement Activation; D005260:Female; D005679:G(M3) Ganglioside / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination
D000907:Antibodies, Bacterial; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D005679:G(M3) Ganglioside; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines