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Abstract

B-cell lymphomas express surface immunoglobulin (immunoglobulin) containing unique idiotypic (idiotype) determinants which may be exploited as tumor specific markers. The inventor has produced murine monoclonal antibodies (MAbs) reactive with the idiotype marker derived from 67 patients with low grade, follicular, small cleaved cell lymphoma. Out of 199 monoclonal antibodies, 47 (24%) were found to react with pooled normal human serum immunoglobulin in concentrations ranging from 0.6 .mu.g/ml to 160 .mu.g/ml. Of these 40 monoclonal antibodies, 90% cross-reacted with idiotype present in normal serum in levels <50 .mu.g/ml. Thirty-two of these anti-idiotypes were directed against a shared idiotope expressed on another patient's lymphoma cells. The frequency of shared idiotope expression defined by each antibody ranged from 0.26% to 3.9% of the B-cell lymphomas tested. A panel of five anti-idiotype antibodies reacted with 80% of AIDS associated lymphomas. Based on the reactivity with these monoclonal antibodies, tumors could be grouped into distinct families. In aggregate, these 32 monoclonal antibodies reacted with a total of 108 of 332 B cell lymphoma cases (32.5%), including 35 of 116 follicular, small cleaved cell lymphomas (30%). Many of these anti-shared idiotopes reacted with more than one histopathologic subtype of lymphoma. Anti-idiotypes have been used in B-cell lymphoma diagnosis and therapy. Moreover, applicant has discovered at least seven anti-shared idiotype antibodies that cross react with autoantibodies, e.g., 16.6 and RF. The development of a library of anti-idiotypes reactive with shared idiotopes should facilitate these clinical studies by obviating the need to develop a customized hybridoma for each patient.

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