Immunohistological reaction mechanism of anti-monosialoganglioside monoclonal antibody, MAb 202, showing predominant cytotoxicity for malignant melanoma.
Mouse monoclonal IgM antibody (MAb 202) can cause melanoma cell necrosis in vivo. We analysed its immune mechanism in three melanoma patients to whom MAb 202 was administered. After the MAb 202 administration, histopathological analysis showed necrosis of melanoma cells expressing only GM3 in two patients. Another patient carrying both GM3 and GD3 showed infiltration of lymphocytes within the tumor nest but no tumor cells or nest necrosis. Immunohistological examination using anti-mouse IgM antibody revealed MAb 202 bound on the surface of melanoma cells in two patients but not in the third (positive for both GM3 and GD3). In vitro, MAb 202 reacted with the melanoma cells of the same two patients, but not with any other tissues of these individuals. We found no reaction of MAb 202 to non-melanoma cells including normal melanocytes and glia cells. Our trials suggest, 1) MAb 202 reacts directly to monosialogangliosides on the melanoma cell surface and then leads to the cytotoxicity reaction, or 2) MAb 202 induces lymphocyte infiltration and possibly then promotes the secretion of some cytokines.
Ota
T
T
Department of Dermatology, Yamaguchi University School of Medicine.
Muto
M
M
Nakano
J
J
Hamanaka
S
S
Irie
R
R
Asagami
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D002465:Cell Movement; D005260:Female; D005732:Gangliosides / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005732:Gangliosides; C025447:sialogangliosides