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

  

Authors:	Gansbacher, B.; Zier, K.; Cronin, K.; Hantzopoulos, P. A.; Bouchard, B.; Houghton, A.; Gilboa, E.; Golde, D.
Article Title:	Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells
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.
Keywords:	human cell; polymerase chain reaction; animal; mice; interleukin 2; melanoma; gene expression; cell line; antineoplastic activity; tumor cells, cultured; transfection; kidney neoplasms; gene transfer; genetic vectors; gene expression regulation, neoplastic; kinetics; gamma interferon; carcinoma, renal cell; mice, nude; vaccination; histocompatibility antigens class i; irradiation; gene therapy; melanoma cell; transplantation, heterologous; effector cell; neoplasm transplantation; tumor rejection; repetitive sequences, nucleic acid; retroviridae; helper cell; interleukin-2; 3t3 cells; major histocompatibility antigen class 1; receptor upregulation; interferon type ii; promoter regions (genetics); adenosine deaminase; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title:	Blood
Volume:	80
Issue:	11
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	1992-12-01
Start Page:	2817
End Page:	2825
Language:	English
PUBMED:	1450408
PROVIDER:	scopus
DOI:	10.1182/blood.V80.11.2817.2817
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026472495&partnerID=40&md5=18b8d7e43ae131d079535b732bbc8dfb
Notes:	Article -- Export Date: 30 July 2019 -- Source: Scopus

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