Lymphokine-activated killer cells were generated from peripheral blood mononuclear cells of 33 patients with liver tumors (benign, 6; primary malignant, 10; metastatic, 17) and 10 healthy individuals. Although peripheral blood mononuclear cell yield was significantly lower (p < 0.01) in patients with hepatocellular carcinoma or with metastatic colorectal cancer, natural killer activity in the peripheral blood mononuclear cell fraction was comparable in all groups tested. Optimal lymphokine-activated killer activity was demonstrated after 9 to 12 days of culture in recombinant interleukin 2. Lymphokine-activated killer activity, interleukin 2induced lymphocyte proliferation and total lytic activity generated per culture in all patient groups studied were similar to those of normal control cells cultured under the same conditions. These in vitro data demonstrate the feasibility of obtaining lymphokine-activated killer cells from the blood of patients with liver tumors and provide a rationale for the future use of lymphokineactivated killer cells in adoptive immunotherapy of pa- tients with primary and metastatic hepatic neoplasms.
Lymphokine-activated killer (LAK) cells can be generated in vitro by culturing of lymphocytes in the presence of crude IL-2 or recombinant interleukin 2 (rIL-2) (1-3). They comprise a population of IL-2-activated cells capable of cytolytic activity against fresh and cultured tumor cell targets but not against normal cells (3, 4). LAK cells have been useful in the adoptive immunotherapy of cancer in animal models ( 5 , 6 ) as well as in clinical trials of patients with advanced metastatic diseases (7, 8). Human renal cell carcinomas and melanomas in advanced stages showed an especially favorable response to LAK plus rIL-2 therapy (7, 8). Like normal individuals, patients with these tumor types were capable of generating in vitro LAK cells with good antitumor activity. Therapy with LAK cells and rIL-2 has already been used in patients with hepatic cancer (9, lo), although little is known about in vitro generation of LAK activity from the circulating mononuclear cells of patients with liver cancer, including primary hepatic tumors as well as