Reduction by anti-antibody administration of the radiotoxicity associated with 131I-labeled antibody to carcinoembryonic antigen in cancer radioimmunotherapy.
Radiolabeled antibodies have been shown to have a therapeutic potential in tumor-bearing animal models. However, treatment with radiolabeled antibodies results in toxic effects to normal tissues, as monitored by losses in body weight and in peripheral wbcs. We have investigated the use of an anti-antibody, or second antibody (SA), as a means of reducing this toxicity. SA rapidly forms a complex with circulating radiolabeled antibody, causing an increase in the clearance rate of the radiolabeled antibody from the blood. Toxicity was significantly reduced in animals given the SA in comparison to the toxicity seen in animals given only the radiolabeled primary antibody (PA). The earlier the SA was administered, the lower was the toxicity. The therapeutic efficacy of radiolabeled antibody was not influenced by the administration of the SA given 48 hours after the PA. Thus, the controlled removal of circulating radiolabeled antibody by an anti-antibody can reduce the toxicity associated with radiolabeled antibody therapy without influencing the antitumor effect.
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
R D
RD
Blumenthal
R M
RM
Sharkey
D
D
Snyder
D M
DM
Goldenberg
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D007167:Immunotherapy; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008647:Mesocricetus; D008657:Metabolic Clearance Rate; D009374:Neoplasms, Experimental / Q000532:radiotherapy / Q000628:therapy*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes