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 x 10(4)/mouse melanoma cells were seen, but not in a group inoculated with 5 x 10(4) 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.
Jinnohara
T
T
Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Tsujisaki
M
M
Sasaki
S
S
Hinoda
Y
Y
Taniguchi
M
M
Imai
K
K
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000627:therapeutic use*; D005260:Female; D005679:G(M3) Ganglioside / Q000276:immunology*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000888:Antibodies, Anti-Idiotypic; D005679:G(M3) Ganglioside; D009363:Neoplasm Proteins