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

Abstract

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). 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. 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. 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.