Suppression of Ehrlich ascites tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype of the anti-GT1b IgM.
Ehrlich tumor expresses the ganglioside GT1b. The plasma of mice with Ehrlich ascites tumor burden also contains GT1b. The structural identity of plasma GT1b was ascertained by a series of enzymatic degradation and mass spectral analysis. Mice were vaccinated with purified plasma GT1b admixed with Freund's adjuvant (FA). Sixty nine percent suppression of Ehrlich ascites tumor growth was observed in vaccinated mice. The suppression was dose-dependent. It is hypothesized that the tumor growth-suppression is a result of immune response to GT1b Humoral immune response to GT1b was demonstrated by passive hemagglutination assay of the sera of vaccinated mice. To test the hypothesis, the mice were administered with rabbit polyclonal anti-GT1b IgM antibody in varying doses and challenged with Ehrlich tumor. A significant reduction in tumor growth (65%) was observed in mice administered with anti-GT1b IgM antibody. Again, the suppression was dose-dependent. To verify further, another batch of mice was immunized with anti-idiotypic antibodies to rabbit anti-GT1b IgM raised in rat. The polyclonal anti-idiotype antibody is expected to carry the structural image of GT1b. In a dose-dependent manner, a maximum of 82% suppression of tumor growth was observed in mice immunized with the anti-idiotype antibody. This observation further strengthened the hypothesis that ganglioside mediated suppression of tumor growth may be a result of immunogenicity of the target ganglioside. This was also supported by positive reaction of the sera of anti-idiotype vaccinated mice with both anti-idiotype antibody and ganglioside GT1b in passive hemagglutination assay. The results favour the therapeutic potential of immunogenic tumor-associated gangliosides.
Saha
S
S
Department of Cell Biology, (Unit of Metabolic Regulation), Chittaranjan National Cancer Institute(CNCI), Calcutta 700026, India.
Mondal
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000737:chemistry; D002240:Carbohydrate Sequence; D002286:Carcinoma, Ehrlich Tumor / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D005732:Gangliosides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D007075:Immunoglobulin M / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D005732:Gangliosides; D007075:Immunoglobulin M; C016481:trisialoganglioside GT1