Specific adoptive immunotherapy of malignant glioma with long-term cytotoxic T lymphocyte line expanded in T-cell growth factor

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Abstract
The purposes of the current study were: (1) to investigate the immunoregulatory effects of T-cell growth factor (TCGF) on the activation and differentiation of syngeneic cytotoxic T lymphocyte (CTL) populations generated against a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma, in C57BL/6 mice; and (2) to determine whether the glioma-specific CTL clone (G-CTLL) could be established by TCGF, and whether thein vivo efficacy of the cloned cells could be rendered more effective in adoptive therapy. It was found that TCGF largely allows the CTL populations to proliferate and thus can activate the depressed cytotoxic activity in tumour-bearing mice. Two lines of G-CTLL were successfully obtained by the limiting dilution technique. The G-CTLL retained a TCGF-dependent proliferative growth and a marked cytotoxic activity with target specificity for over 18 months, characterized by a surface phenotype of Lyt-1−·2·3+, Lyt-2 antibody blocking of cytotoxicity and the production of immune interferon in response to mitogen and tumour antigen. In the Winn assay and the adoptive transfer assay, the therapeutic effects were detected in intracranially inoculated tumours in mice. Thein vivo efficacy was dependent on the dose of G-CTLL and on the time of the intravenous administration, although the transfer was inversely ineffective in conditions of increased intracranial pressure. The mechanism responsible for thein vivo effect was probably due to the adoptive immunity and/or the tumour-specific interferon production of G-CTLL.