A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant-dependent and non-transient antitumour activity against B16 mouse melanoma in vitro and in vivo.
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| Abstract |
The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vaccines. Recently, we hydrophobically incorporated purified GM3 into the outer membrane protein complex from Neisseria meningitidis to form very small size proteoliposomes (GM3/VSSP). We have examined the antitumour properties of GM3/VSSP vaccine and compared it with GM3 incorporated in very low density serum lipoproteins (GM3/VLDL). Immunization with four doses of GM3/VSSP vaccine (120 microg of ganglioside) plus Freund's adjuvant or Montanide ISA 51 significantly increased the overall survival of mice inoculated in the subcutis with 103 B16-F1 cells, whereas the GM3/VLDL immunogen was ineffective. The non-transient character of tumour protection was confirmed in animals surviving the first challenge and re-inoculated with 5 x 103 cells. GM3/VSSP vaccine also reduced the subcutaneous growth of highly aggressive B16-F10 cells. The importance of ganglioside structure in the tumour-protective effect of GM3/VSSP vaccine was confirmed using GM3 containing N-glycolylneuraminic acid, a ganglioside absent in melanoma cells. Immunostaining and enzyme-linked immunosorbent assay (ELISA) experiments showed a high specificity of immune sera against GM3 and the presence of all four IgG subclasses, with a preponderance of IgG2b and IgG3. In addition, a strong anti-B16 complement-mediated cytotoxicity was induced by vaccination with GM3/VSSP. The present data indicate the molecular specificity of GM3/VSSP vaccine as well as the adjuvant-dependent and non-transient character of tumour protection in the B16 mouse model. These findings suggest that an appropriate GM3 vaccine may be capable of inducing prolonged tumour protection in melanoma patients.
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| Authors | A Carr, Z Mazorra, D F Alonso, C Mesa, O Valiente, D E Gomez, R Perez, L E Fernandez |
| Journal | Melanoma research (Melanoma Res) Vol. 11 Issue 3 Pg. 219-27 (Jun 2001) ISSN: 0960-8931 [Print] England |
| PMID | 11468510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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