Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells

B. Gansbacher, K. Zier, K. Cronin, P. A. Hantzopoulos, B. Bouchard, A. Houghton, Eli Gilboa, D. Golde

Research output: Contribution to journalArticle

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Abstract

Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon γ (IFN-γ), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-γ cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-γ-containing vectors and secreted IL-2 at 1 to 40 U/mL/106 cells/24 h or IFN-γ 1 to 8 U/mL/106 cells/24 h, respectively. After γ irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-γ induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine-containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after γ irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.

Original languageEnglish
Pages (from-to)2817-2825
Number of pages9
JournalBlood
Volume80
Issue number11
StatePublished - Dec 1 1992
Externally publishedYes

Fingerprint

Gene transfer
Interferons
Interleukin-2
Melanoma
Cytokines
Genes
Cells
Tumors
Neoplasms
Irradiation
Cell Line
Lymphocytes
Lymphocyte Activation
Major Histocompatibility Complex
Heterografts
Modulators
Vaccination
Up-Regulation
Complementary DNA
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Gansbacher, B., Zier, K., Cronin, K., Hantzopoulos, P. A., Bouchard, B., Houghton, A., ... Golde, D. (1992). Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells. Blood, 80(11), 2817-2825.

Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells. / Gansbacher, B.; Zier, K.; Cronin, K.; Hantzopoulos, P. A.; Bouchard, B.; Houghton, A.; Gilboa, Eli; Golde, D.

In: Blood, Vol. 80, No. 11, 01.12.1992, p. 2817-2825.

Research output: Contribution to journalArticle

Gansbacher, B, Zier, K, Cronin, K, Hantzopoulos, PA, Bouchard, B, Houghton, A, Gilboa, E & Golde, D 1992, 'Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells', Blood, vol. 80, no. 11, pp. 2817-2825.
Gansbacher B, Zier K, Cronin K, Hantzopoulos PA, Bouchard B, Houghton A et al. Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells. Blood. 1992 Dec 1;80(11):2817-2825.
Gansbacher, B. ; Zier, K. ; Cronin, K. ; Hantzopoulos, P. A. ; Bouchard, B. ; Houghton, A. ; Gilboa, Eli ; Golde, D. / Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells. In: Blood. 1992 ; Vol. 80, No. 11. pp. 2817-2825.
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