Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: Comparison of immunologic properties with interleukin-2

A. R. Miller, W. H. McBride, S. M. Dubinett, G. J. Dougherty, J. D. Thacker, H. Shau, D. B. Kohn, R. C. Moen, M. J. Walker, R. Chiu, B. L. Schuck, J. A. Rosenblatt, M. Huang, S. Dhanani, K. Rhoades, J. S. Economou

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Two human melanoma cell lines were transduced with the human interleukin (IL)-7 and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level cytokine expression was achieved. The in vitro growth of transduced tumors was unaltered. Neither of the IL-2-transduced melanoma cell lines grew in athymic mice, whereas one IL-7-transduced melanoma line showed retarded in vivo growth. This is consistent with animal studies suggesting a predominantly T-cell response to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced tumors. Both IL-7- and IL-2-transduced melanoma cell lines could induce cytotoxic lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In one cell line, IL-7 transduction resulted in a marked inhibition of the immunosuppressive peptide transforming growth factor (TGF)β1. The results allow a comparison of immunobiologic properties of IL-7-and IL-2-transduced human melanoma cell lines in consideration of their use in genetically engineered tumor vaccines. IL-7 transduction results in stable cytokine expression and phenotypic alterations that appear to be favorable for enhanced immunogenicity and it deserves clinical testing.

Original languageEnglish (US)
Pages (from-to)3686-3694
Number of pages9
JournalBlood
Volume82
Issue number12
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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