ADOPTIVE IMMUNOTHERAPY WITH TUMOR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 IN PATIENTS WITH METASTATIC MALIGNANT-MELANOMA AND RENAL-CELL CARCINOMA - A PILOT-STUDY

Purpose: The objective of this study was to determine the tolerance an d effect of moderate-dose recombinant human interleukin-2 (rHu IL-2) a nd tumor-infiltrating lymphocytes (TIL) in patients with metastatic me lanoma (MM) or renal cell carcinoma (RCC) refractory to standard thera py. Patients and Methods: Twenty-six patients (18 MM and eight RCC) we re entered onto this pilot study. TIL were isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3, for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2 alanine 125 (r-met Mu IL-2 [ ala-125]). At least 10(10) TIL were reinfused intravenously in three d ivided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000 U/kg of IL-2 per injection was administered every 8 hours fr om day 2 through day 11 for a total of 28 doses. Results: Sixteen mela noma patients completed the study. Of these, three (19%) showed a dura ble complete response (CR), nine (56%) had no response (NR), and four (25%) had progressive disease (PD). One nonresponder demonstrated comp lete tumor regression within 1 year of treatment. Of four assessable R CC patients, two experienced a minor response (MR) and two showed NR. All TIL cultures showed comparably high cytotoxic activity as determin ed by antibody-redirected lysis (ARL). More importantly, melanoma TIL from responders possessed significantly higher cytotoxicity against au tologous tumor cells than TIL from nonresponders (P < .05). Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), interfe ron gamma (IFN-gamma), interleukin-6 (IL-6), tumor necrosis factor alp ha (TNF-alpha), and IL-4 was similar for TIL from melanoma responders and nonresponders, or TIL from RCC patients. Conclusion: Immunotherapy with polyclonally activated TIL and moderate-dose IL-2 could be succe ssfully used for the treatment of immunogenic tumors with less toxicit y and lower costs as compared with high-dose IL-2 protocols. J Clin On col 13:1939-1949. (C) 1995 by American Society of Clinical Oncology.