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  • Cell-Based Therapy
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Cell-Based Therapy

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

Gene Therapy volume 7, pages 837–843 (2000)Cite this article

Abstract

Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-effects. However, genetically engineered tumor cells secreting cytokines still induce toxicity and activate bystander cells. To circumvent such problems, membrane-bound forms of IL-4 (IL-4m) were expressed on MethA fibrosarcoma tumor cells. Chimeric forms of IL-4 with the type I transmembrane protein CD4 or type II transmembrane protein TNF were designed to express IL-4 in opposite orientations on the tumor cell surface. The IL-4m on tumor clones was able to support cell growth of the IL-4 dependent cytotoxic cell line (CT.4S) and the Th2 cell clone (D10). Furthermore, the IL-4m tumor clones stimulated proliferation of 2C TCR transgenic spleen cells which are responsive to Ld MHC class I molecules. Expression of the IL-4/TNF chimeric protein on MethA cells elicited antitumor immunity and protected from MethA tumor challenge. The proposed tumor vaccine may serve as an effective gene therapy method to avoid the toxicity of recombinant cytokines and bulk bystander leukocyte stimulation encountered in conventional cytokine gene therapy.

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Acknowledgements

The authors thank Drs Soon-Cheol Hong (Medical College of Ohio, OH) and Sang-Young Chun (Chonnam National University) for providing for CD4 and TNF cDNAs; Drs Charles Janeway jr (Yale University), and Peter Cresswell (Yale University) for providing anti-IL-4 and anti-MHC class I antibodies; and Mr Stephen Maher (Yale University) and Dr Jung Kyu Park (Chungnam National University) for assistance with FACS analysis. This work was supported by grant (KOSEF: 94–0403–14–02–3) to YSK and GM46367 from NIH to AB.

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Authors and Affiliations

  1. Department of Biochemistry, College of Natural Sciences, Institute of Biotechnology, Chungnam National University, Republic of Korea

    Y S Kim & C H Sonn

  2. Department of Biology, College of Natural Sciences, Institute of Biotechnology, Chungnam National University, Republic of Korea

    S-G Paik

  3. Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA

    A L M Bothwell

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Kim, Y., Sonn, C., Paik, SG. et al. Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity. Gene Ther 7, 837–843 (2000). https://doi.org/10.1038/sj.gt.3301175

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