Immunogene therapy of murine fibrosarcoma using IL-15 gene with high translation efficiency

Keiko Kimura, Hitoshi Nishimura, Kenji Hirose, Tetsuya Matsuguchi, Yuji Nimura, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    We have recently found that translational efficiency is up-regulated by an alternative exon in IL-15 mRNA in mice. In a malignancy model using BALB/c mice and syngeneic Meth A fibrosarcoma (Meth A), we successfully applied immunological gene therapy with IL-15 protein using alternative IL-15 cDNA with high translational efficiency. Two expression vectors carrying the murine IL-15 gene were constructed for use in tumor immunotherapy, one utilizing IL-15 cDNA with alternative exon 5 and the second utilizing IL-15 cDNA with normal exon 5. The first vector induced the production of a large amount of IL-15 protein in Meth A cells, whereas tumor cells transfected by the second vector produced only a marginal level of IL-15 protein. Although cell growth of both transfectants in vitro remained unchanged, inoculation of clones transfected with normal IL-15 cDNA resulted in progressive tumor growth, while clones transfected with alternative IL-15 cDNA led to the rejection of the tumor. The clone producing high levels of IL-15 grew progressively in nude mice and mice treated with anti-CD4 monoclonal antibodies (mAb), whereas the growth of the transfectants was retarded in anti-CD8 mAb- or anti-asialo GM1 antibody-treated mice. Cured mice were shown to have generated immunity against a subsequent challenge with the wild type of Meth A but not against Meth 1 tumor cells, another type of fibrosarcoma derived from BALB/c mice. Thus, tumor therapy based on IL-15 gene transfection was effective against Meth A tumor cells, suggesting a possible application to human neoplasms.

    Original languageEnglish
    Pages (from-to)1532-1542
    Number of pages11
    JournalEuropean Journal of Immunology
    Volume29
    Issue number5
    DOIs
    Publication statusPublished - May 25 1999

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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