Brain tumors are generally resistant to killing by cytotoxic effectors of the immune system including cytotoxic T- lymphocytes (CTL). Incubation of lymphocytes with recombinant interleukin-2 (IL-2), however, generates lymphokine activated killer cells (LAK) endowed with tumoricidal capacity. Rodents innoculated intracranially with autologous glioblastoma cells exhibit increased survival when treated with IL-2. This phenomenon is believed to occur due to the infiltration of tumor by LAK generated in vivo. LAK have been generated in vitro which produce lysis of autologous and allogeneic tumor tissue but not normal PBL. We have compared various routes of administration of IL-2 and LAK to assure optimal delivery of lymphokine and killer cells to obtain a favorable therapeutic effect. Patients receiving IL-2 experience toxic side effects associated with the extravasation of intravascular fluid and the development of a vascular leak syndrome. We have shown that a product of lymphocytes activated in vitro with IL-2 produces a similar phenomenon when tested in a modified """"""""Miles"""""""" assay. This substance is macromolecular in nature and is the product of lymphocytes or mononuclear cells.
