Effects of methotrexate-carcinoembryonic-antigen-antibody immunoconjugates on GW-39 human tumors in nude mice.
Methotrexate (MTX) was conjugated to an anti-carcinoembryonic antigen monoclonal antibody (NP2) by using amino-dextran as an intermediate carrier. The drug was chemically linked to amino-dextran (average Mr = 40,000), and the resulting MTX-dextran was then site-specifically attached to the carbohydrate moiety of the antibody. Athymic nude mice that carried human colonic GW-39 tumors (s.c.) were treated with the immunoconjugate. In this study, the specific conjugate caused a greater inhibition of the tumor growth than either free MTX or its conjugate with dextran and an irrelevant antibody. The intermediate MTX-dextran and the unlinked mixture of MTX-dextran with NP2 were both relatively ineffective in inhibiting tumor growth. The greatly reduced host toxicity permitted the use of the MTX-dextran-NP2 in a high-dose therapy of this tumor system.
Shih
L B
LB
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D003911:Dextrans / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D009368:Neoplasm Transplantation
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003911:Dextrans; D000922:Immunotoxins; D008727:Methotrexate