Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse γ-interferon complementary DNA

• Published in: Cancer research (Chicago, Ill.) Ill.), 1988-09, Vol.48 (17), p.4730-4735
• Main Authors: NISHIHARA, K, MIYATAKE, S, SAKATA, T, YAMASHITA, J, KIKUCHI, H, KAWADE, Y, YOULI ZU, NAMBA, Y, HANAOKA, M, WATANABE, Y
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens, Surface - analysis; Biological and medical sciences; Cell Line; DNA - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glioma - immunology; Immunobiology; Immunotherapy; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Male; Mice; Mice, Inbred C57BL; Organs and cells involved in the immune response; Retroviridae - genetics; T-Lymphocytes, Cytotoxic - immunology; Transfection
• ISSN: 0008-5472; 1538-7445

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse gamma-interferon (IFN-gamma) into a specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced mouse glioma line) and confirmed the efficacy of IFN-gamma production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 to 10 times the amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203 glioma than the parental cells; the enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, and asialo-GM1-. The surface expression of a major histocompatibility complex Class I antigen, H-2Kb, was not altered remarkably, but the Class II antigen, I-Ab, was partially and slightly enhanced on the two IFN-gamma-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-gamma producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-gamma, the cells may be stimulated to induce or enhance the expression of surface antigens including major histocompatibility complex antigens as well as tumor-associated antigens relevant to immune recognition. The 203 glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. Taken together, the results suggested that the augmented specific tumor-killing activity of our gene-transferred cytotoxic T-lymphocytes was ascribed to the constitutive production of IFN-gamma derived from the exogenous gene.