| First Author | Kimura K | Year | 1999 |
| Journal | Eur J Immunol | Volume | 29 |
| Issue | 5 | Pages | 1532-42 |
| PubMed ID | 10359107 | Mgi Jnum | J:55318 |
| Mgi Id | MGI:1337710 | Doi | 10.1002/(SICI)1521-4141(199905)29:05<1532::AID-IMMU1532>3.0.CO;2-Z |
| Citation | Kimura K, et al. (1999) Immunogene therapy of murine fibrosarcoma using IL-15 gene with high translation efficiency. Eur J Immunol 29(5):1532-42 |
| abstractText | 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. |
