DIAGNOSIS OF AND THERAPY FOR SOLID TUMORS WITH RADIOLABELED ANTIBODIES AND IMMUNE FRAGMENTS

Abstract

Antibodies which are directed against human tumor-associated antigens can potentially be used as carriers of radioactivity for in vivo diagnosis (radioimmunodetection) or treatment (radioimmunotherapy) of solid tumors, including colon, hepatoma, cholangiocarcinoma and melanoma. Murine monoclonal antibodies (MOAB), produced by the hybridoma technique of Kohler and Milstein, are replacing conventional heterosera as sources of antibodies, because MOAB can be produced in large quantities as reproducible reagents with homogeneous binding properties. Human melanoma was studied using MOAB IgG and Fab fragments that recognize the human melanoma-associated antigens p97 and high MW antigen. Both antigens are found in the membrane of melanomas at much larger concentrations than in normal adult tissues. Radioimmunodetection studies were performed with whole Ig, 88% of lesions > 1.5 cm were detected. Fab fragments were used for radioimmunotherapy; large doses of radiolabeled antibodies (up to 342 mCi) can apparently be repetitively given to patients without excessive end-organ toxicity. Two of 3 patients treated with high-dose-radiolabeled antimelanoma Fab showed an effect from the treatment. Although both technical and biologic problems remain, the use of radiolabeled antibodies that are directed tumor-associated antigens holds future promise as a new therapeutic approach to solid tumors that are resistant to conventional therapy.