Augmentation of Tumor Targeting in a Line of Glioma-specific Mouse Cytotoxic T-Lymphocytes by Retroviral Expression of Mouse γ-Interferon Complementary DNA

摘要: As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse γ-interferon (IFN-γ) into specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced line) and confirmed the efficacy of IFN-γ production from exogenous gene on augmentation tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 10 times amount as compared with parental E-4. Correspondingly, these exhibited 2 3 higher killing activity than cells; enhancement activities was abrogated by adequate addition anti-IFN-γ antibody. No alteration seen after transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, asialo-Gm1-. The expression major histocompatibility complex Class I antigen, H-2Kb, not altered remarkably, but II I-Ab, partially slightly enhanced IFN-γ-producing sublines mentioned above fluorescence-activated sorter analysis. Since it is considered that vicinity producing are exposed high concentration IFN-γ, may be stimulated induce or enhance antigens including well tumor-associated relevant immune recognition. pretreated were more efficiently killed both E-4 sublines. Taken together, results suggested augmented tumor-killing our T-lymphocytes ascribed constitutive derived gene.