Site-directed tumor chemotherapy.
The therapeutic effect of drugs used in cancer chemotherapy has been augmented by their complexing or chemical linking to macromolecular carriers. The role of the carrier should be to deliver the drug preferentially to the tumor site. Potential carriers are either (1) nonspecific macromolecules whose preferential activity is due to the inherently higher permeability and pinocytic activity of tumor cells, (2) lysosomotropic agents such as DNA or liposomes, or (3) the more specific agents--antitumor antibodies. Conjugates of daunomycin to antitumor antibodies, prepared either by direct binding or by binding via dextran, were shown to retain both the antibody and the drug activity. Thus they exert specific cytotoxic activity toward tumor cells that the antibodies recognize. In vivo, these complexes are more active than the free drug in prolongation of survival of mice transplanted with the tumor cells. Conjugates of daunomycin with normal immunoglobulin or with dextran also show higher therapeutic efficacy in vivo, probably due to their capacity to reduce the cytotoxicity of daunomycin and/or to the higher permeability of neoplastic cells. But under certain conditions, mainly at low drug concentrations, the drug-antibody conjugates have an advantage over all others.
D000818:Animals; D000912:Antibodies, Neoplasm; D003630:Daunorubicin / Q000627:therapeutic use; D006801:Humans; D007942:Leukemia, Experimental / Q000276:immunology; D008223:Lymphoma / Q000276:immunology; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy*; D010954:Plasmacytoma / Q000276:immunology
D000912:Antibodies, Neoplasm; D003630:Daunorubicin