We plan to continue our monoclonal antibody studies on human melanomas towards the development of pre-clinical immunotherapeutical procedures for melanoma. There are 4 Specific Aims: 1. To continue our characterization of cell surface antigens of human melanomas by using monoclonal mouse antibodies. Our major effort will go into obtaining antibodies to antigens expressed by (malignant) melanoma but not by (benign) nevi. As part of this project, we shall look for antibodies distinguishing the two major subtypes of melanoma (nodular, superficial spreading) and - to the extent logistically possible - for antibodies distinguishing primary and metastatic melanoma. We shall also investigate the extent to which various melanoma-associated antigens (p97, a proteoglycan, a GD3 ganglioside, as well as the """"""""new"""""""" antigens identified under Aim #1) are expressed in cells from human fetuses. 2. To obtain anti-idiotypic antibodies to human melanomas by using monoclonal mouse antibodies as immunogens and to use these antibodies to probe the immunological repertoire of melanoma patients;
under Aim #4 the antibodies will also be used as immunogens in mice. 3. To test the ability of anti-melanoma antibodies to destroy human melanomas xenografted to nude mice. The effect of antibody alone, and antobody combined with an immunomodulator (e.g., BCG or C-parvum) will be investigated as part of this. 4. To use a model, in which the genes for p97 or the proteoglycan antigen are inserted into mouse tumor cells, to study anti-tumor effects, first, of passive immunization with anti-p97 antibody and, second, of active immunization with cells, antigens or anti-idiotypic antibodies.
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