[Clinical studies of adoptive immunotherapy of human disseminated brain tumors with LAK cells and recombinant interleukin-2]

Abstract

In previous in vitro studies, the authors showed that recombinant interleukin-2 (rIL-2) stimulated peripheral blood lymphocytes (PBL) from patients with malignant brain tumors to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. We then tried the adoptive transfer of such lymphokine-activated killer-(LAK) cells induced from patients with meningeal gliomatosis (MG) and meningeal carcinomatosis (MC). PBL fractions were separated into a plastic bag by leukophoreses using HEMONETICS V 50. PBL were then harvested by LSM (Litton Bionetics, Kensington, Md.) gradient centrifugation according to the standard method. Human LAK cells were generated by placing 5 X 10(7) PBL in 10-cm diameter plastic dishes (Falcon) holding 20 ml of complete medium (CM) containing 100 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI P640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml of gentamicin sulfate, 0.03% glutamine and 2% heat-inactivated human AB serum. The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks' balanced salt solution (HBSS) and resuspended in HBSS for transfer to patients. 1-2 X 10(8) LAK cells were injected intrathecally through Ommaya's reservoir or a V-P shunt reservoir twice a week. Portions of LAK cells were tested for cytotoxicity in vitro. During the adoptive transfer of LAK cells, patients were given intravenous injections of 500 units of rIL-2 every day. Case 1: A 29-year-old man with meningeal gliomatosis.(ABSTRACT TRUNCATED AT 250 WORDS)