An experimental approach to specific adoptive immunotherapy for malignant brain tumors
Yamasaki, T.; Kikuchi, H.
Nihon Geka Hokan. Archiv für Japanische Chirurgie 58(6): 485-492
1989
ISSN/ISBN: 0003-9152 PMID: 2519184 Document Number: 340585
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-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma). Furthermore, the cloned CTL lines 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 exogeneous 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. It was thus suggested that the killing mechanism may be associated with the direct lytic activity of CTL cloned cells or the tumor-specific production of gamma IFN by the clones.