Experience in the preparation and experimental use of immunocytostatics.
Vindesine (VDS) was coupled directly to a monoclonal antibody (791T/36) raised against a human osteogenic sarcoma cell line, and methotrexate (MTX) was coupled to 791T/36 via an intervening human serum albumin (HSA) bridge. Both the VDS-791T/36 and MTX-HSA-791T/36 conjugates were cytotoxic in vitro specifically for tumour target cells expressing the 791T/36-defined antigen, while the free drug in each case was indiscriminately toxic to all target cells. The VDS-791T/36 conjugate retarded growth of osteogenic sarcoma xenografts in immunodeprived mice when administered in multiple doses. Free 791T/36 did not significantly affect tumour growth. VDS was tumour inhibitory, but was toxic to the mice at a total dose of 20 micrograms per kg body weight, while VDS-791T/36 conjugate was not toxic at total doses incorporating VDS at up to 45 mg per kg. It is suggested that this is due to selectivity conferred upon the conjugate by the antibody moiety, and that such conjugates may offer considerable potential as anti-cancer agents.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008727:Methotrexate / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000031:analogs & derivatives / Q000276:immunology; D014751:Vindesine
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014747:Vinblastine; D014751:Vindesine; D008727:Methotrexate