g(m2)-ganglioside and Lymphoma

The structure of the major gangliosides from murine lymphoma EL-4 was established by acid hydrolysis, methanolysis, methylation analysis, neuraminidase treatment and chromium trioxide oxidation. Two of these gangliosides were identified as the N-acetyl and N-glycoloyl forms of the GM2 ganglioside. The third ganglioside making up to 40% of the total ganglioside pool contained two sialic acid residues and was identified as a GD2 ganglioside which up to now had not been reported in extraneural tissues.

Topics: Animals; Ascitic Fluid; Chromatography, Thin Layer; Fatty Acids; G(M2) Ganglioside; Gangliosides; Lymphoma; Mice; Mice, Inbred C57BL; Sialic Acids

Mice challenged with L5178Y lymphoma cells expression high levels of the glycolipid asialo GM2 (gangliotriosylceramide) were protected from tumor growth by passive administration of a monoclonal antibody specific for the glycolipid; in a few antibody-treated mice, ascites cells eventually proliferated which contained a reduced chemical quantity of the glycolipid antigen (3). We now report that the cells emerging from antibody-treated mice had abnormal marker chromosomes identical to those in the cells used for challenge, indicating that the emergent cells were progeny of the challenge inoculum. Flow cytometric analysis revealed that asialo GM2 was undetectable on the surface of greater than 95% of the tumor cells from antibody-treated mice, whereas surface display of H-2 determinants was unchanged from that of the cells used for challenge. Tumor cells arising in challenged but untreated mice consisted of a mixture of asialo GM2-positive and -negative cells, indicating the presence of selective pressures in these mice as well. None of the cells taken from tumor bearing mice differed significantly from the challenge cells in their susceptibility to natural killer cell attack, suggesting that resistance to natural killer cell lysis was not responsible for the proliferation of these cells in vivo. When cells derived from an antibody-treated mouse were used to challenge mice, serotherapy with anti-asialo GM2 had no effect on mouse survival. These results suggest that serotherapy may complement a host anti-tumor response, from which only asialo GM2 deficient cells can escape.

Topics: Animals; Antibodies, Neoplasm; Antigens, Neoplasm; G(M2) Ganglioside; Glycolipids; Immunotherapy; Lymphoma; Male; Mice; Neoplasms, Experimental; Sialic Acids