Immunotherapy Using 41BB Selected Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

Background: * Autologous tumor infiltrating lymphocytes (TIL) followed by high dose aldesleukin can mediate the regression of bulky metastatic melanoma when administered to a patient following a non-myeloablative but lymphodepleting chemotherapy preparative regimen. * In animal models, mixing irrelevant (non-reactive) cells with tumor-reactive cells negatively impacts on tumor treatment possibly by competing for cytokines, suggesting that enrichment for tumor-reactive cells could enhance clinical efficacy. Additionally, preclinical animal models and clinical investigation have demonstrated that prolonged in vitro culture negatively impacts on tumor treatment. * The current method for enrichment of tumor-reactive TIL requires screening of multiple independent TIL cultures for anti-tumor specificity using gamma-interferon production by TIL. However, in vitro screening depends on autologous tumor reagents that are often unavailable, and interferon (IFN) gamma release in vitro may not be the best effector function to evaluate tumor recognition. The screen increases the length of in vitro culture times (30 days), which results in shorter telomere lengths and more differentiated cells. Additionally, selection of a few highly reactive cultures for further expansion may reduce the diversity of cluster of differentiation 8 (CD8+) repertoire recognizing the tumor. * 4-1BB is a co-stimulatory molecule up-regulated on the cell surface of T cells upon T-cell receptor (TCR) engagement. Pre-clinical studies in the Surgery Branch have evaluated a fast and simplified method to select and expand a diverse tumor-reactive repertoire, regardless of knowledge of the specific antigen recognized, based on selection of 4-1BB expressing TIL from the fresh tumor digest. Objectives: * To determine the safety and objective response rate of patients with metastatic melanoma receiving ACT using 4-1BB selected TIL plus aldesleukin treatment following a chemotherapy preparative regimen. * To determine the survival of patients receiving this treatment regimen. Eligibility: Patients who are 18 years or older must have: * Evaluable metastatic melanoma; * Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL; * No contraindications to high-dose aldesleukin administration; * No concurrent major medical illnesses or any form of immunodeficiency Design: * Patients with metastatic melanoma will have a lesion resected and 4-1BB expressing tumor infiltrating lymphocytes will be isolated using a fluorescence-activated cell sorting (FACS) sorter approved for clinical use. The 4-1BB selected cells will be rapidly expanded in vitro and administered plus aldesleukin following a non-myeloablative chemotherapy preparative regimen. * The study will be conducted using a stage 2 optimal design to determine if this treatment is able to be associated with a clinical response rate that can rule out 10% (p0=0.10) in favor of a modest 30% partial response (PR) + complete response (CR) rate (p1=0.30). * Up to 35 patients may be enrolled over 2 years.