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

Y. S. Kim, C. H. Sonn, S. G. Paik, A. L.M. Bothwell

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 L(d) 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.

Original languageEnglish (US)
Pages (from-to)837-843
Number of pages7
JournalGene Therapy
Volume7
Issue number10
DOIs
StatePublished - May 2000
Externally publishedYes

Keywords

  • IL-4
  • Immunotherapy
  • Tumor immunity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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