Development of a human xenograft model for the evaluation of monoclonal antibody L6-mitomycin immunoconjugates.
The human lung carcinoma H2981, was characterized as a preclinical model for evaluating immunoconjugates consisting of monoclonal antibody (MAb) L6 and drugs of the mitomycin (MMC) chemotype. The H2981 tumor, implanted subcutaneously in athymic, mice grew progressively in greater than 95% of recipients. Spontaneous regressions of established tumors were not observed. The administration of tolerated doses of MMC resulted in dose-dependent delays in tumor growth. The incidence of tumor regressions was low indicating the potential to observe increased efficacy with immunoconjugates. The antitumor effects of MMC were independent of the schedule and route of administration. MAb L6 delayed the outgrowth of tumors when administered 24 h after tumor implant. Antitumor activity was not observed when MAb L6 was administered to mice bearing established tumors. The efficacy of mixtures of MAb L6 and optimal doses of MMC was not significantly better than that of optimal doses of MMC given alone.
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Bristol-Myers Co., Wallingford, CT 06492.
Rose
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D000922:Immunotoxins; D016685:Mitomycin