RESEARCH FOR CLINICAL APPLICATION OF ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES.

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1) Detection of anti-melanoma antibodies in serum of melanoma patients. High molecular weight-melanoma associated antigen (HMW-MAA) is one of human melanoma associated antigen and is thought to be poorly immunogenic. In this study we have developed new system to detect for the anti-HMW-MAA antibodies in serum of melanoma patients using anti-idiotypic monoclonal antibodies (anti-Id mAb) to anti-HMW-MAA mAb. In this new system, anti-HMW-MAA antibodies were found in 20% and 40% of serum of melanoma patients with stage 1 and 4 respectively and was not found in healthy normal control. These results suggest that HMW-MAA could elicit the immune response in some melanoma patients.2) Immunogenicity of anti-Id mAb. The anti-Id mAb, which bears the internal image of HMW-MAA, was injected into BALB/C mouse three times and serological and immunochemical analysis was done using mouse serum. The serum reacted only cultured melanoma cell. Furthermore, serum immunoprepicitate the same band from radiolabeled melanoma cells with anti-HMW-MAA mAb on SDS-PAGE.Cultured melanoma cells were injected into the right foot pad which mouse already immunized with anti-Id mAb and culture lymphoid cells were injected into the left side as control. Swelling of foot pad were measured and anti-Id mAb can induce the delayed type hypersensitivity.These results suggest that anti-Id mAb can induce both humoral and cellular immune response against the HMW-MAA.3) Immunohistochemistry for anti-anti-Id mAb. Anti-anti-Id mAb were developed from the mouse immunized anti-Id mAb which bears the internal image of HMW-MAA. The anti-anti-Id mAb display similar reactivity patterns with surgically removed melanoma lesions.