INDUCTION OF HUMAN AUTOLOGOUS CYTOTOXIC T-LYMPHOCYTES AGAINST MINCED TISSUES OF GLIOBLASTOMA-MULTIFORME

The authors induced autologous cytotoxic T lymphocytes (CTLs) directly from peripheral blood lymphocytes by preparing a coculture of minced tissue fragments of glioblastoma multiforme (GBM) with interleukins-1, -2, -4, and -6 and interferon-gamma in RHAM alpha medium containing 5 % autologous plasma for 2 weeks. At the end of this period, the freque ncies of CD3+, CD4+, CD8+, and CD16+ lymphocytes were 95% to 99%, 40% to 62%, 37% to 38%, and 0.2%, respectively. The lymphocytes killed 82% to 100% of the GBM cells within 48 hours at an effector-to-target cel l ratio of 1.67, whereas in a separate coculture, autologous lymphokin e-activated killer (LAK) cells killed only 33% of GBM cells under the same conditions. The lymphocytes showed no cytotoxicity against LAK-se nsitive Daudi cells, natural killer-sensitive K562 cells or autologous fibroblasts grown from the brain tumor, although they did show slight cytotoxicities against allogeneic GBM cell Lines. These results lead the authors to suggest that the lymphocyte population contains specifi c CTLs for autologous brain tumor cells and that these CTLs could be e ffective in adoptive immunotherapy to combat brain tumor.