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

Kiyoshi Nishihara, Shinichi Miyatake, Junkoh Yamashita, Haruhiko Kikuchi, Yoshimi Kawade, Yoshihiko Watanabe, Youli Zu, Yuziro Namba, Masao Hanaoka, Tsuneaki Sakata

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse 7-interferon (IFN-γ) 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-γ production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred sub-clones constitutively produced 8 to 10 times the amount of IFN-γ 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-γ 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-γ-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-γ producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-γ, 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-γ 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-γ derived from the exogenous gene.

Original languageEnglish (US)
Pages (from-to)4730-4735
Number of pages6
JournalCancer research
Volume48
Issue number17
StatePublished - Sep 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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