Combination of lymphokine‐activated killer cells and interleukin‐2 in treating metastatic renal cell carcinoma

OBJECTIVE: To study the properties of lymphokine-activated killer (LAK) cells and the effect of immunotherapy with a combination of autologous LAK cells and interleukin-2 (IL-2) [LAK therapy] in 10 patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: The LAK cells were generated from peripheral blood lymphocytes (PBL) by incubation in a serum-free medium (AIM-V) supplemented with IL-2 for 4 days and killer cells were administered intravenously twice a week. The LAK cells showed cytotoxicity against allogenic RCC cell lines and augmented NK and LAK activities. Their phenotypes were CD25+, HLA-DR+, CD3+, and CD16+. Furthermore, LAK cells released IFN-gamma, IL-1 beta, and TNF-alpha. The total number of LAK cells administered ranged from 3.8 x 10(9) to 52.6 x 10(9) cells and the total amount of IL-2 ranged from 150 x 10(5) to 900 x 10(5) U. The effect on pulmonary metastasis in response to LAK therapy was studied. RESULTS: The outcome was complete response (1), partial response (1), minor response (2), no change (4) and disease progression (2). Toxic effects were transient and no serious side-effects occurred. Evaluation of host immune parameters indicated that a clinical response was expected in patients with increasing proportions of CD16+, CD25+, CD57+, HLA-DR+ and CD3+DR+ cells among PBL and with augmentation of NK and LAK activities. Brain metastases were detected in three patients during or after treatment. CONCLUSION: LAK therapy appears to be effective in treating some patients with RCC and pulmonary metastasis. The potential for inducing brain metastasis, however, should be taken into account.