An experimental approach to specific adoptive immunotherapy for malignant brain tumors

With the aid of interleukin 2 (IL-2), two phenotypically different cytotoxic T lymphocyte (CTL) clones were established with target specificity against syngeneic murine malignant brain tumor (a methylcholanthrene-induce ependymoblastoma of C57BL/6 mouse origin, 203-glioma). Furthermore, the cloned CTL lines were characterized in vitro, and their in vivo effectiveness was investigated by intracerebral (i.c.) tumor neutralization assay and adoptive immunotherapy with the clones for i.c. tumor-bearing mice. Each CTL clone retained an IL-2 dependency with a defined functional activity. G-CTLL 1 with a phenotype of Lyt-1-.2.3+ exhibited a target cytotoxicity against 2 kinds of murine glioma cells, syngeneic 203-glioma and allogeneic RSV-M glioma (Schmitt-Ruppin rous sarcoma virus-induced malignant astrocytoma). It is noted that G-CTLL 1 cells produced gamma interferon (IFN) by stimulation with glioma antigens. The spontaneous release of gamma IFN paralleled the amounts of exogenous IL-2 added into the cultures, but IL-2 had no synergistic effects on IFN release in the presence of tumor antigens. Furthermore, by adding anti-mouse gamma IFN antibody, the IFN production of G-CTLL 1 cells was inhibited but their lytic potential was hardly reduced in vitro. In contrast, G-CTLL 2 cells expressed a cell surface phenotype of Lyt-1+.2.3+ with more restricted target specificity against only syngeneic 203-glioma cells, although they showed a weaker cytotoxicity than G-CTLL 1 cells and no release of gamma IFN. The in vivo therapeutic efficacy using G-CTLL 1 cells was confirmed in both adoptive immunotherapy and tumor neutralization assays.(ABSTRACT TRUNCATED AT 250 WORDS)