Anti-tumor effect of internal image bearing anti-idiotypic monoclonal antibody in relation to GM3 ganglioside

Anti-idiotypic antibodies are a new type of useful tools for the possible treatment of cancer patients, since some act as antigen specific immunomodulators. Anti-idiotypic monoclonal antibody (anti-Id MAb) D704 (Ab2) was established which bore the internal image of the determinant defined by MAb M2590 (Ab1) against a sialic acid residue on GM₃ ganglioside. In an in vivo syngeneic tumor system, anti-Id MAb D704 was more effective in preventing tumor progression, as compared with anti-GM₃ MAb or no treatment. Significant suppression of tumor growth and prolongation of survival by administration of anti-Id MAb D704 in an animal group inoculated with 1 × 10⁴/mouse melanoma cells were seen, but not in a group inoculated with 5 × 10⁴ cells/mouse. In an active specific immunotherapy protocol utilizing Ab2, the activity of anti-anti-Id antibodies (Ab3) specific for GM₃ (antigen) which has a weak immunogenicity only, was maintained for more than 3 months. Ab2 generated cellular anti-tumor immune responses, including delayed type hypersensitivity (DTH) reaction. Immunohistological analysis indicated a marked infiltration of CD4 and CD8 positive cells into the DTH sites. Our results suggest that internal image bearing anti-Id MAbs have a therapeutic potential against tumors if the number of melanoma cells is relatively low or if hosts are at an early stage of melanoma progression. Int. J. Cancer 76:345–353, 1998. © 1998 Wiley-Liss, Inc.