The results of a phase I clinical trial in progress have shown that immunization with murine monoclonal antiidiotypic antibodies which bear the mirror image of human high molecular weight-melanoma associated antigen (HMW-MAA) is not associated with any side effect, in spite of the development of anti mouse Ig antibodies. Furthermore, immunization with antiidiotypic monoclonal antibodies may have a beneficial effect on the clinical course of the disease in some patients. These results justify a continuation of these investigations. Since the immunogenicity of murine antiidiotypic monoclonal antibody (MoAb) MK2-23 (an internal image of HMW-MAA) is markedly enhanced by conjugation to a carrier and by administration with an adjuvant, this proposal aims at characterizing the cellular and humoral anti HMW-MAA immunity in patients with melanoma induced by MoAb MK2-23 conjugated with KLH and mixed with BCG and at correlating the parameters of the immune response with the clinical course of the disease. Furthermore, antibody secreting EBV-transformed B lymphoid cell lines will be originated from the immunized patients. Utilizing serological and immunochemical assays, antibodies which mimic the specificity of murine MoAb MK2-23 and anti HMW-MAA MoAb 763.74 (used to elicit MoAb MK2-23) will be identified. The corresponding cell lines will be used as a source of RNA to determine the sequence of the heavy and light chain variable regions of the human anti HMW-MAA antibodies and corresponding antiidiotypic antibodies. The resulting information will be compared to the available data about the heavy and light chain variable region sequences of the corresponding murine idiotypic and antiidiotypic antibodies to characterize sequences essential to antigen mimicry and to identify sequences necessary for antigen recognition. These investigations will contribute to our understanding of the molecular mechanisms underlying the beneficial effect of immunotherapy with antiidiotypic antibodies on the clinical course of the disease.
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