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Comparative Study
. 1996 Apr 2;93(7):2909-14.
doi: 10.1073/pnas.93.7.2909.

Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy

H Fakhrai  1 , O Dorigo, D L Shawler, H Lin, D Mercola, K L Black, I Royston, R E Sobol
Affiliations
Comparative Study

Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy

H Fakhrai et al. Proc Natl Acad Sci U S A. .

Abstract

Like human gliomas, the rat 9L gliosarcoma secretes the immunosuppressive transforming growth factor beta (TGF-beta). Using the 9L model, we tested our hypothesis that genetic modification of glioma cells to block TGF-beta expression may enhance their immunogenicity and make them more suitable for active tumor immunotherapy. Subcutaneous immunizations of tumor-bearing animals with 9L cells genetically modified to inhibit TGF-beta expression with an antisense plasmid vector resulted in a significantly higher number of animals surviving for 12 weeks (11/11, 100%) compared to immunizations with control vector-modified 9L cells (2/15, 13%) or 9L cells transduced with an interleukin 2 retroviral vector (3/10, 30%) (P < 0.001 for both comparisons). Histologic evaluation of implantation sites 12 weeks after treatment revealed no evidence of residual tumor. In vitro tumor cytotoxicity assays with lymph node effector cells revealed a 3- to 4-fold increase in lytic activity for the animals immunized with TGF-beta antisense-modified tumor cells compared to immunizations with control vector or interleukin 2 gene-modified tumor cells. These results indicate that inhibition of TGF-beta expression significantly enhances tumor-cell immunogenicity and supports future clinical evaluation of TGF-beta antisense gene therapy for TGF-beta-expressing tumors.

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References

    1. J Immunol. 1986 Jan;136(2):728-31 - PubMed
    1. Hum Gene Ther. 1995 May;6(5):591-601 - PubMed
    1. Science. 1986 Aug 1;233(4763):532-4 - PubMed
    1. Cell. 1987 May 22;49(4):437-8 - PubMed
    1. EMBO J. 1987 Jun;6(6):1633-6 - PubMed

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