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Development of anti-idiotype monoclonal antibodies for Sialyl Le(a) antigen.

Anti-idiotype monoclonal antibodies (MoAbs) were developed for a carbohydrate antigen, Sialyl Le(a), by immunizing mice with an anti-Sialyl Le(a) MoAb, KM231 (mouse IgG1). The anti-idiotype MoAbs inhibited the binding of KM231 to Sialyl Le(a)-positive mucin protein, but did not affect the binding of another MoAb (mouse IgG1) which recognized a peptide epitope on the same mucin protein. The selected four anti-idiotype MoAbs bound to all of the five anti-Sialyl Le(a) MoAbs examined, but not to other MoAbs developed against Sialyl Le(a)-related carbohydrate antigens such as Le(a), Le(x), and Sialyl Le(x) blood type A, B, H antigens. Immunization of rats with one of the anti-idiotype MoAbs, of which the reactivity was remarkably inhibited by Sialyl Le(a) oligosaccharide, resulted in the induction of antibody (Ab3) to purified Sialyl Le(a) glycolipid. Taken together, one of the anti-idiotype MoAbs developed in this study was the first Ab2 beta-type anti-idiotype MoAb which carried the internal image of Sialyl Le(a) antigen. The positive reaction of tumor cells expressing Sialyl Le(a) antigen with the Ab3 gave rise to the possibility that the anti-idiotype MoAb would become an effective tool for active immunotherapy in patients with Sialyl Le(a)-positive tumor.