The design of cytotoxic-agent-antibody conjugates.
The rationale for the use of antibodies as carriers of cancer chemotherapeutic agents is based upon: the presence on cells of tumor-associated cell surface antigens (TAA); the ability to obtain specific polyclonal or monoclonal antibodies against them; and the availability of methods for binding appropriate toxic agents or radionuclides with retention of activity of both antibody and agents. The general finding so far has been that both conventional polyclonal and hybridoma-derived monoclonal antibodies can deliver cytocidal amounts of toxic agents to target tumor cells both in vitro and in vivo. Moreover, various agents with different modes of antitumor activity (e.g., DNA intercalation or alkylation, enzyme inhibition, and cell surface modification) have all produced superior tumor inhibition in conjugate form compared to the individual or synergistic inhibition produced by agent and antibody. Recent studies are contributing to the understanding of the mechanism of action of drug-antibody conjugates and are thus establishing guidelines for this approach to cancer therapy.
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000918:Antibody Specificity; D000951:Antigens, Neoplasm; D001761:Bleomycin / Q000627:therapeutic use; D002699:Chlorambucil / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use; D009279:Naphthacenes / Q000627:therapeutic use; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D011485:Protein Binding; D011868:Radioisotopes / Q000627:therapeutic use; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014751:Vindesine / Q000627:therapeutic use; D009353:Zinostatin / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D008937:Mitomycins; D009279:Naphthacenes; D011868:Radioisotopes; D001761:Bleomycin; D002699:Chlorambucil; D016685:Mitomycin; D009353:Zinostatin; D014751:Vindesine