Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-gamma in oral cancer patients

Abstract

Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon-gamma (IFN-gamma) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2 x 10(5) U/m2) and rIFN-gamma (7.0 x 10(4) U/m2), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16+CD57+ and CD16+CD57- NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3+HLA-DR+, CD8+Leu8-, and CD4+Leu8- cells. Significant increases in NK activity, from the original level of 32.0 +/- 13.7 to 49.9 +/- 15.2%, and LAK activity, from 4.8 +/- 3.5 to 11.0 +/- 6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3- and CD16- cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3- cells (31.1 +/- 14.3%). At Day 7, NK activity of CD16- cells increased up to 21.4 +/- 14.9%, accompanied by an increase in CD3(-)-cell activity (54.5 +/- 20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5 +/- 5.6 and 9.4 +/- 6.6% in CD16- and CD3- cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O2-generation was significantly increased, from the original 81.1 +/- 28.1 to 95.6 +/- 34.9 pmol/min/10(4) cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN-gamma is thought to be useful in cancer treatments.