Immune Responses Induced by Anti-idiotypic Antibody against Anti-DU-PAN-2 Antibody and its application to Diagnosis and Therapy of Cancer

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Using monoclonal antibody (mAb) DU-PAN-2 as immunogen, we prepared polyclonal anti-idiotypic antibody (pId) in a rat and syngeneic monoclonal anti-idiotypic antibody (mId) by hybridoma technique. Since pId and mId reacted specifically with mAb DU-PAN-2 and inhibited the specific binding of DU-PAN-2 (D-2) antigen and mAb DU-PAN-2, mId and a certain portion of pId were considered to possess the mirror image of the determinant on the antigen defined by mAb DU-PAN-2. Immunization of syngeneic mice with mId induced anti-anti-Id antibodies (Ab3) which inhibited the binding of mAb DU-PAN-2 to the D-2 antigen. Moreover, Ab3 could not induced CDC activity and CTL, but ADCC activity.An enzyme-linked immunosorbent assay (ELISA) utilizing these anti-idiotypic antibodies was developed and was used to examine the clinical significance of levels of circulating antibody against D-2 antigen in sera of cancers. With the mean + 2 SD of healthy controls regarded as the cutoff value, levels exceeded this value in 42% of cancer patients by pId assay, and in 33% by mId assay. The falsepositive rate of mId assay in benign diseases was 21% which was significantly lower than that of the pId assay (45%). No significant correlation between serum D-2 antigen and anti D-2 antibody was observed in the sera of cancer patients. 43% (pId assay), and 31% (mId assay) of the antigen negative cancer patients showed antibody levels exceeding the cutoff values. All of 12 patients with gastric or colonic cancer classified as histological stage I were negative for D-2 antigen, while 4 patients (33%) were antibody positive by pId assay. Anti-D-2 antibody fraction which was purified from the serum of a cancer patient by pId immunoaffinity chromatography, reacted with both D-2 antigen and mId as determined by various immunochemical techniques. Measurement of serum levels of anti-D-2 antibody may be useful in detecting malignancies including early of antigen-negative cancers.