Autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes(NCI)

Background:
Melanoma antigen recognized by T cells (MART-1) is a gene that is present in melanoma cells.
This study tests an experimental treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified with a gene called anti-MART-1 transduced cells (F5) to target and destroy their tumor. Some of the cells are given as an infusion and others are given as a vaccine.
The anti-MART-1 F5 cells are currently being studied in other patients in combination with chemotherapy and IL-2 (aldesleukin) therapy.
Objectives:
-To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to shrink tumors and to prevent melanoma from recurring.
Eligibility:
Patients 18 years of age and older whose melanoma has been removed and are currently disease-free, but who are at risk for recurrence.
Patients who do not have ocular or mucosal melanoma.
Patients with tissue type human leukocyte antigens (HLA-A)*0201).
Design:
Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and leukapheresis, a procedure for collecting white cells to modify in the laboratory and later reinfuse into the patient.
Patients are assigned to one of four study groups:
Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day 0.
Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1 vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG. The vaccine is repeated on day 30.
Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose IL-2 for 5 days (days 0-4).
Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and low-dose IL-2 for 5 days. The vaccine is repeated on day 30.
Recovery: Patients are monitored closely and given medicines to prevent or treat any side effects of therapy.
Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect cells to examine the effects of the treatment on the immune system.
Follow-up: Patients return to National Institutes of Health (NIH) 35 days after completing treatment and then at 3 months and every 6 months thereafter for evaluation with a physical examination, review of side effects, laboratory tests and scans. They have blood tests at 3, 6 and 12 months after treatment and then once a year after that. A biopsy may be requested after treatment ends to examine the effects of treatment on the immune system. All patients return to NIH for a physical examination once a year for 5 years and then complete a follow-up questionnaire for another 10 years.

Background:
Melanoma antigen recognized by T-cells (MART)-1 is a protein present in melanoma cells.
An experimental procedure developed for treating patients with melanoma uses the anti-MART-1 F5 gene and a type of virus to make special cells called anti-MART-1 F5 cells that are designed to destroy the patient's tumor. These cells are created in the laboratory using the patient's own tumor cells or blood cells.
The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) MART-1, made from a virus that ordinarily infects canaries and is modified to carry a copy of the MART-1 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti-MART-1 F5 cells.
Objectives:
-To evaluate the safety and effectiveness of anti-MART-1 F5 and the ALVAC vaccine in treating patients with advanced melanoma.
Eligibility:
-Patients 18 years of age with metastatic melanoma for whom standard treatments have not been effective.
Design:
Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment.
Patients have 7 days of chemotherapy to prepare the immune system for receiving the anti-MART-1 F5.
Patients receive the ALVAC vaccine, anti-MART-1 F5 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti-MART-1 F5 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of anti-MART-1 F5 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses.
After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.