T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Melanoma

Background: * A T cell receptor (TCR) that recognizes the NY-ESO-1 (ESO) tumor/testes antigen has been cloned into a retrovirus and can be used to genetically modify human peripheral blood lymphocytes (PBL) so they recognize human leukocyte antigen (HLA)-A2+, ESO+ tumors * PBL expressing the anti-ESO TCR have been administered with aldesleukin with or without ALVAC vaccine to 21 patients with melanoma following lymphodepleting chemotherapy at the Surgery Branch, resulting in objective tumor regression (complete or partial regression) in ten patients (47%). * In animal models using murine cells and in experiments with human T cells in vitro, T cell subsets expressing the lymphoid homing and differentiation marker cluster of differentiation 62L (CD62L), including na(SqrRoot) ve T cells (TNaive), stem cell memory T cells (TSCM), and central memory T cells (TCM), were shown to have superior attributes compared to whole PBL and CD62L- PBL for adoptive cell therapy, including superior persistence following transfer in vivo. Objectives: Primary objective: \- To determine whether the administration of anti-ESO TCR engineered CD62L+-derived lymphocytes plus high-dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen can result in an objective regression rate (partial response (PR) + complete response (CR)) of melanoma tumors. Secondary objectives: * Determine the persistence of genetically engineered, adoptively transferred CD62L+ derived lymphocytes. * Determine the toxicity profile of this treatment regimen. Eligibility: Patients who are: * Human leukocyte antigen (HLA)-A\*0201 positive * 18 years of age or older * Have metastatic melanoma that expresses the ESO antigen Patients may not have: \- Contraindications for high dose aldesleukin administration. Design: * Peripheral blood mononuclear cells (PBMC) will be obtained by leukapheresis and will undergo positive selection for CD62L using a CliniMACS magnetic cell separation apparatus to enrich for the less differentiated TNaive, TSCM, and TCM subsets. * The enriched CD62L+ lymphocytes will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth, then transduced with the anti-ESO TCR. * All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine. * On day 0 patients will receive anti-ESO TCR gene-transduced CD62L+ -derived lymphocytes and then begin high dose aldesleukin. * A complete evaluation of evaluable lesions will be conducted 6 weeks (+/- 2 weeks) following the administration of the cell product. * The primary objective will be efficacy. The study will be conducted using a phase II optimal design (Simon R, Controlled Clinical Trials 10:1-10, 1989) in order to rule out an unacceptably low 40% overall response rate (p0=0.40) in favor of an improved response rate of 65% (p1=0.65). This study will initially enroll 11 evaluable patients, and if 0 to 5 of the 11 have a response, then no further patients will be accrued. If 6 or more of the first 11 patients have a response, then accrual would continue until a total of 20 patients have been enrolled. If there were 11 or more responses in 20 patients (55%), this would be sufficiently interesting to warrant further study in later trials. To allow for a very small number of inevaluable patients, the accrual ceiling will be set at 22 patients.