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. 1990 Jul;31(4):197–201. doi: 10.1007/BF01789168

Effects of methotrexate-carcinoembryonic-antigen-antibody immunoconjugates on GW-39 human tumors in nude mice

Lisa B Shih 1, David M Goldenberg 1,✉
PMCID: PMC11038486  PMID: 1696173

Abstract

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 (averageM r = 40000), 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.

Keywords: Tumor Growth, Methotrexate, Dextran, Nude Mouse, Human Tumor

Footnotes

Supported in part by U.S.P.H.S. grant CA39 841 from the NIH

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