Biologic Response to Intracavitary Interleukin-2/Lymphokine Activated Killer (IAK) Cells in the Treatmemt of Primary Malignant Brain Tumors

Abstract

A Phase I trial of intracavitary recombinant Cetus IL-2 and lymphokine-activated killer (IAK) cells was performed in 9 adult patients (pts) with recurrent glioma with Karnofsky scores ≦ 60; 8 pts Grade IV, 1 pt Grade III. Following leukapheresis, lymphocytes were activated ex vivo. Activated IAK and IL-2 were infused via an Ommaya reservoir implanted in the tumor cavity during reqperation. Repetitive bolus IL-2 was given MWF for two weeks (wks). This cycle was repeated 2 wks later and in similar 4 wk courses every 12 wks for pts with anti-tumor response or stable disease. Corticosteroid therapy was limited to treatment of IL-2 related CNS toxicity. There was no evidence of systemic toxicity, nor were changes observed in peripheral immunophenotypes. The reservoirs were aspirated prior to each infusion and analyzed. A progressive eosinophilia was noted in the aspirates in a cumulative IL-2 dose-dependent manner, with apparent priming between cycles. Lumbar CSF punctures obtained in two cases also demonstrated eosinophilia. Similarly, IL-2 levels increased in the aspirates in a cumulative dose related manner. Tissue specimens, obtained in 5 pts after therapy, demonstrated pericavitary necrosis with an eosinophilic infiltrate and perivascular mononuclear cells. There were two partial responses. The median survival for 8 pts with Grade IV tumors was >50 wks, with 3 pts still alive.