Phase 1/2 Study of Metastatic Renal Cancer Using T-Cells Transduced With a T-Cell Receptor Which Recognizes TRAIL Bound to the DR4 Receptor

Background: * The clinical administration of tumor-reactive T-cells grown in vitro is a highly active therapy for patients with metastatic melanoma in experimental protocols when they are combined with preparative lymphodepleting chemotherapy and systemic IL-2. * We cloned a novel T-cell from the blood of a patient with renal cell cancer (RCC), which recognizes nearly all human renal cancer lines irrespective of MHC haplotype. * The alpha sign and beta sign chain of T-cell receptor from this clone, 2G-1, can be introduced into human lymphocytes by retroviral transduction and confers this same recognition of RCC. * This TCR was found to recognize TNF-related apoptosis inducing ligand (TRAIL) bound to its receptor DR4. * Both TRAIL and agonist antibodies to DR4 have tumor specificity and are in current clinical trials for cancer. * Two amino acid modifications of the native TCR greatly augmented its recognition of RCCs without altering background reactivity. Objectives: * Primary: * Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC. * To identify the maximum tolerated dose (MTD) for cells incorporating a TCR in PBL and in TIL. * Secondary: * Determine the toxicities of these T-cells administered in the above fashion. * Determine TCR and vector presence in the post treatment phase. Eligibility: * Patients with measurable metastatic clear cell renal cancer who have previously received at least one systemic standard care regimen and have progressed or be found to be intolerant of standard therapies. * Patients must be eligible for high-dose IL-2. * Patients must not have active or clinically symptomatic CNS metastases within the previous 3 months. * Patients must have acceptable hematopoietic and major organ function as determined by laboratory and/or functional testing. Design: * A phase I-II dose escalating protocol with 2 arms. Patients in Arm A will receive peripheral blood lymphocytes transduced with the 2G-1 TCR; patients in Arm B will receive renal TIL transduced with the 2G-1 TCR. Arm B will begin after a safe dose has been defined in Arm A. * Once MTD has been established for each arm, up to 24 patients will be enrolled in each arm of the phase II stage. * Patients will receive a nonmyeloablative but lymphocyte-depleting preparative regimen consisting of cyclophosphamide and fludarabine followed in one to four days by IV infusion of their transduced cells and subsequent IV aldesleukin administration. * Up to 106 patients may be enrolled over 3-4 years.