ANALYSIS OF MELANOMA IDIOTYPE NETWORK AND IT'S APPLICATION FOR VACCINE THERAPY.

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(1) Immunohistochemical analysis of idiotype network in melanomaThe mouse anti-id mAb MK2-23 bears the internal image of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.8 HMW-MAA binding anti-anti-id Mabs elicited with mAb MK2-23 were characterized in their reactivity with a large panel of surgically removed benign and malignant melanocytic tumors. The 8 anti-anti-id mAbs displayd subtle differences in their immunoperoxidase staining of both benign and malignant tumors. The diversity in the fine specificity of the 8 anti-anti-id mAbs is likely to reflect the few somatic mutations which occur in the amino-acid sequence of the variable regions of their heavy and light chains in the course of the immune response to mAb MK2-23. The reactivity patterns of the 8 anti-anti-id mAbs with the tissue substrates are similar, although not superimposable upon that of the anti-HMW-MAA mAb 763.74 elicited with melanoma cells. This defference may reflect the imperfect mimicry by anti-id mA … More b MK2-23 of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.Moreover the amino-acid sequences of 8 anti-anti-id mAbs were compared with that of anti-HMW-MAA mAb 763.74.80-95% and 85-100% homology were seen in the amino-acid sequence of the variable regions of their heavy and light chains, respectively. The highest homology was found in CDR1 and lowest in CDR3.(2) Production of anti-melanoma antibodies with anti-Id mAbAdministration of anti-Id mAb elicites anti-anti-Id mAb reacting with human melanoma cells. For the improvement of this efficacy, administration with adjuvant of anti-Id mAb MK2-23 conjugated to a carrier induces more efficiently to anti-anti-Id antibodies reacting with human melanoma cells. Moreover, F (ab') 2 fragment and chimeric mAb MK2-23 were found to reduce the anti-mouse antibodies in rabbit, which may cause the unfaborable side effect.(3) Mechanism of loss of HLA class I in melanoma lesionsThe aim of this study was to investigate the expression of HLA Class 1 antigens in surgically removed melanoma lesions. To this end 32 primary and 11 metastatic lesions were stained in the immunoperoxidase reaction with monoclonal antibodies (mAb) to monomorphic, locus specific and polymorphic antigenic determinants. The intensity of staining of melanoma cells was compared to that of keratinocytes surrounding the tumor nest. The patients' HLA phenotype was determined utilizing the conventional lymphocytotoxicity assay. About 20% of primary and about 50% of metastatic lesions were not stained or were stained with reduced intensity by mAb to monomorphic and locus specific antigenic determinants. Moreover about 40% of primary and about 60% of metastatic lesions were not stained or were stained with low intensity, by mAb to HLA Class 1 allospecificities. These results indicate that the frequency of abnormalities in HLA Class 1 antigen expression is high in melanoma lesions. These abnormalities are likely to have a negative impact on T cell based immunotherapy, since they provide melanoma cells with a mechanism to escape from destruction by cytotoxic T cells. Less