The objective of this proposal is to conduct indepth studies of tumor invasion and metastasis in two human tumor systems, malignant melanoma and neuroblastoma. This will be accomplished by two major approaches: First, by gaining a basic understanding of the complex processes at the biological and molecular levels, using at least five different antigens preferentually expressed on these neoplasms and already will established as effective targets for tumor destruction mediated by specific monoclonal antibodies. Second, by first optimizing and them combining individual treatment modalities to act synergistically in the destruction of human tumors and their mestastases in experimental animal model systems. These effects will combine manipulations of the host's immune system with targeting of chemotherapeutic drugs, radionuclides, differentiation agents and ribosome inactivating proteins (RIP) by monoclonal antibodies directed to effective tumor antigen targets. The basic rationale underlying this research proposal is to make use of monoclonal antibody-defined antigens on human melanoma and neuroblastoma cells that have already been established as effective targets for monoclonal antibody-mediated tumor destruction during the last five years of this laboratory's efforts. To render these systems optimally effective approaches will be used to gain further basic knowledge of tumor invasion and metastasis. Other experimental systems will be optimized with reagents and treatment modulities being combined to act most synergystically in the destruction of human melanoma and neuroblastoma metastases. It is anticipated that achievement of the objectives outlined here will result in a better understanding of tumor biology and hopefully provide new and effective modalities for the treatment of human cancer.
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