Conjugates of monoclonal antibody 791T/36 with methotrexate in cancer therapy

The design and evaluation of drug-antibody conjugates for tumor therapy is considered with respect to the use of the anti-human osteogenic sarcoma monoclonal antibody designated 791T/36. Conjugates have been constructed by linking antibody to methotrexate; the agent has been linked to antibody, either directly or via a human serum albumin bridging agent. In each case, conjugates have been assessed for retention of antibody reactivity with osteogenic sarcoma target cells by comparing their capacity with that of unmodified antibody in competing with fluorescein isothiocyanate-labeled 791T/36 binding, as measured by flow cytometry. Retention of drug cytotoxicity was evaluated by in vitro cytotoxicity and colony inhibition assays. Conjugates with acceptable retention of drug and antibody reactivities were then examined for in vivo suppression of human tumor xenografts.