Study of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and interleukin-2 for metastatic renal cell carcinoma. I. Generation of LAK cells by incubation in serum-free medium

Abstract

Investigation into the clinical application of LAK cells for treating renal cell carcinoma was carried out. LAK cells were induced from peripheral blood mononuclear cells of healthy adults or renal cell carcinoma patients by incubation of peripheral blood mononuclear cells in complete medium (RMPI1640 containing 10% heat-inactivated human AB serum) or serum-free medium (AIM-V) supplemented with IL-2. Then the characteristics of the LAK cells thus produced were studied. When cultured in complete medium, peripheral blood mononuclear cells isolated from healthy adults, recovered to 60% of the initial level on day 4 of incubation. Both NK and LAK activity were markedly enhanced before day 4. On day 4, a similar number of peripheral blood mononuclear blood cells and a similar cytotoxicity were observed in serum-free culture. The cells with a high growth rate during the 4 days of incubation were CD25, HLA-DR, CD3, CD16 cells in both cultures. The supernatant of LAK generation cultures had detectable levels of interferon (IFN)-gamma, interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha on day 4. IFN-gamma and IL-1 beta both showed significant concentrations in the LAK culture supernatant, which increased progressively with further culture. TNF-alpha was not produced by LAK cells alone. IFN-gamma and IL-beta production by the LAK cells was enhanced by stimulation with the Caki-1, ACHN and K-562 tumor cell lines, while TNF-alpha production was stimulated by Caki-1 and K-562 cells.(ABSTRACT TRUNCATED AT 250 WORDS)