This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metastic melanoma and renal cell carconoma are incurable malignancies with an average survival of less than one year. Immune stimulation with interleukin (IL)-2 has demonstrated some efficacy in the treatment of these cancers. Vaccination has also been explored as a treatment that boosts antitumor T cell responses in melanoma, as well as renal cell carcinoma. A novel form of tumor immunotherapy involves the administration of tumor antigen on the surface of cell-sized (5 micron diameter) microspheres. Antigen, in the form of proteins or cell membranes, displaced on silica microspheres provide an effective stimulus for antigen-specific cytotoxic T lymphocytes (CTL) activation that results in tumor cell killing. This form of antigen presentation is termed Large Multivalent Immunogen (LMI). Vaccination of tumor-bearing mice with tumor membrane-coated LMI resulted in significant regression of malignant lesions. The primary objective of this study is to test the safety of autologous tumor membrane-coated LMI in the treatment of patients with metastic melanoma and renal cell carcinoma. Patients undergoing surgical resection of a tumor or affected lymph nodes for diagnosis and staging or for palliation of symptoms will be eligible to participate. Membranes from tumor cells are siloated from the resected tissue and attached to 5-micron silica beads. A single dose of the chemotherapy drug Cytoxan, which inhibits suppressor T cells that may prevent an adequate immune response to vaccination is given on day 1. LMI is administered on day 8 and 36. Daily subcutaneous IL-2 is given for week 1. 5 days after the LMI doses on days 13-20 and 41-48. The first 6 patients receive Cytoxan and LMI alone to evaluate the safety of this combination. Subsequent patients (up to 30) will be treated with Cytoxan, vaccine, and one of four dose levels of IL-2 in order to determine the safety of these agents together. The secondary objective is to determine whether an immune response is generated following vaccination, although this study is not designed to determine the statistical significance of such a response. Cytokine production by circulating CTL and the delayed-type hypersensitivity (DTH) reaction will determine immune response before and after vaccine administration. These data will provide insight into the mechanisms of tumor immunology in those patients with advanced melanoma and renal cell carcinoma. The GCRC will administer Cytoxan, the vaccine and IL-2 injections, and will draw research blood samples from patients. Further, skin test for DTH reactions will be performed in the GCRC.
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