Intralesional Infusion of Lymphokine-activated Killer (LAK) Cells and Recombinant Interleukin-2 (rIL-2) for the Treatment of Patients with Malignant Brain Tumor

Abstract

Abstract Twenty patients with supratentorial, intracerebral lesions defined by computed tomographic scan or magnetic resonance imaging were treated by surgery and adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant Interleukin-2 (rIL-2, Cetus). Seventeen patients had glioblastoma, two had high-grade oligodendroglioma, and one patient had two metastatic sarcoma lesions. LAK cells were produced from blood mononuclear cells (MNC) obtained by 2 to 3 leukapheresis procedures and cultured (2.5 × 106 MNC/ml) 3 to 5 days with 1000 units rIL-2/ml. Although LAK cells could be produced from MNC of all patients, those taking steroids or with a low Karnofsky functional status generated, on average, suboptimal LAK cell activity. Age, sex, and serum anticonvulsant levels do not seem to influence a patient's ability to produce LAK cells in vitro. For therapy, cultured MNC (1-15 × 109) containing LAK cells were suspended in saline containing 106 units rIL-2 and injected into tissue surrounding the tumor cavity during craniotomy. For 3 days after their operations, patients received 106 units rIL-2 into the tumor cavity through an Ommaya reservoir. The treatment protocol was tolerated well by all patients, although they all experienced some degree of headache, fever, or lethargy that cleared within a few days of the last rIL-2 injection. When computed tomographic (CT) scans were obtained soon after treatment, areas of low density suggested a greater-than-normal extent of edema around the operative site. At the present time, CT scans indicate that the tumors of seven patients have recurred with an average disease-free interval of 25 ± 6 weeks. Eight patients have remained alive and free of tumor for at least 6 months after surgery and immunotherapy. LAK cell plus rIL-2 immunotherapy for brain tumors is safe and may be efficacious against minimal tumor burden.