Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen.
Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.
Ghose
T
T
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrone
S
S
Blair
A H
AH
Kralovec
Y
Y
Temponi
M
M
Singh
M
M
Mammen
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D008727:Methotrexate