ANTIIDIOTYPIC RESPONSE AGAINST MURINE MONOCLONAL-ANTIBODIES REACTIVE WITH TUMOR-ASSOCIATED ANTIGEN TAG-72

The immune response of 42 gastrointestinal and ovarian cancer patients at 1 month after exposure to murine monoclonal antibodies (B72.3 and CC49) reactive with the tumor-associated antigen TAG-72 was studied. T he incidence of human anti-mouse antibody response was 89% to B72.3 an d 70% to CC49. To evaluate the antiidiotypic immune response, we devel oped a serological assay based on affinity chromatography to remove th e interference due to the presence of TAG-72, antiisotypic, and antial lotypic immunoglobulins in the serum. Seventy-eight percent of patient s who received B72.3 developed an antiidiotypic response; in 33% of th e patients, this was the only immune response detected. The antiidioty pic immune response after treatment with CC49 was present in 54% of th e patients. Twelve percent of the patients who received CC49 developed an antiidiotypic response in the absence of antiisotypic or antiallot ypic immune response. The lower immunogenicity of the variable region of CC49 is encouraging when considering the use of chimeric or humaniz ed antibodies derived from the murine monoclonal antibody CC49 in clin ical studies.