Table 1.
Patient demographics, treatments received, and clinical outcomes.
| Patient | Age/sex | Treatment* |
Sites of evaluable metastases | Response duration (months)∥ | Autoimmunity | |||
|---|---|---|---|---|---|---|---|---|
| Cells infused†(× 10-10) | CD8/CD4 phenotype‡(%) | Antigen specificity§ | IL-2 (doses) | |||||
| 1 | 18/M | 2.3 | 11/39 | Other | 9 | Lymph(axillary, nodes mesenteric, pelvic) | PR¶ (24 +) | None |
| 2 | 30/F | 3.5 | 83/15 | MART-1, gp100 | 8 | Cutaneous, subcutaneous | PR (8) | Vitiligo |
| 3 | 43/F | 4.0 | 44/58 | gp100 | 5 | Brain, cutaneous, liver, lung | NR | None |
| 4 | 57/F | 3.4 | 56/52 | gp100 | 9 | Cutaneous, subcutaneous | PR (2) | None |
| 5 | 53/M | 3.0 | 16/85 | Other | 7 | Brain, lung, lymph nodes | NR-mixed | None |
| 6 | 37/F | 9.2 | 65/35 | Other | 6 | Lung, intraperitoneal, subcutaneous | PR (15 +) | None |
| 7 | 44/M | 12.3 | 61/41 | MART-1 | 7 | Lymph nodes, subcutaneous | NR-mixed | Vitiligo |
| 8 | 48/M | 9.5 | 48/52 | gp100 | 12 | Subcutaneous | NR | None |
| 9 | 57/M | 9.6 | 84/13 | MART-1 | 10 | Cutaneous, subcutaneous | PR (10 +) | Vitiligo |
| 10 | 55/M | 10.7 | 96/2 | MART-1 | 12 | Lymph nodes, cutaneous, subcutaneous | PR¶ (9+) | Uveitis |
| 11 | 29/M | 13.0 | 96/3 | MART-1 | 12 | Liver, pericardial, subcutaneous | NR-mixed | Vitiligo |
| 12 | 37/F | 13.7 | 72/24 | MART-1 | 11 | Liver, lung, gallbladder, lymph nodes | NR-mixed | None |
| 13 | 41/F | 7.7 | 92/8 | MART-1 | 11 | Subcutaneous | NR | None |
Each patient was treated with chemotherapy (27) starting 7 days before cell administration, consisting of 2 days of cyclophosphamide at 60 mg per kg of body weight, followed by 5 days of fludarabine at 25 mg/m2. On the day after the final dose of fludarabine, when circulating lymphocyte and neutrophil counts had dropped to less than 20/mm3, each patient received an intravenous infusion of autologous lymphocytes over approximately 30 to 60 min. After cell infusion, patients received high-dose IL-2 therapy consisting of 720,000 IU/kg by bolus intravenous infusion every 8 hours to tolerance (10). Some patients with mixed or responding lesions received an additional course of cell transfer therapy.
T cell cultures for infusion were derived from TILs by minor modifications of established techniques (2, 5). Multiple cultures were started from each resected melanoma specimen and were screened independently by cytokine secretion assay for recognition of autologous tumor cells (if available) and HLA-A2tumorcell lines ( 11). TIL cultures that exhibited specific tumor cell recognition were expanded for treatment using one or two cycles of a rapid expansion protocol (28) with irradiated allogeneic feeder cells, OKT3 (anti-CD3) antibody, and 6000 IU perml of IL-2.
Percent of lymphocyte gated cells from the infusion sample that stained with each antibody. Values do not add to 100% if a significant fraction of infused cells was double negative ordouble positive forCD4 and CD8 antigen expression.
Antigen specificity was determined by cytokine release assay (11). Other: recognition of autologous tumor cells but no HLA-A2-restricted epitope derived from MART-1, tyrosinase, tyrosinase related protein 1 (TRP1), TRP2, NY-ESO-1, gp100, MAGE1, orMAGE3.
NR, no response; PR, partial response.
Microscopic residual focus of disease resected; patient remains free of disease (11). Patient 1 had a 6-mm brain density that increased to 8 mm at 8 months. After localized stereotactic radiotherapy, the density disappeared.