Cytokine gene transduction into non-immunogeneic murine tumor cells.
The effect of cytokine transduction on the tumorigenicity and immunogenicity of murine non-immunogeneic mammary carcinoma (4T1), acute myeloid leukemia (mAML) and partially immunogenic B-cell leukemia (BCL1) has been evaluated in syngeneic strains of mice. Transduction by retroviral vectors containing the genes for GM-CSF, IL-2 or IFN-gamma did not lead to a marked antitumor effect in 4T1 mammary tumor or BCL1. A reduced local tumor size was observed in mice inoculated with 4T1 cells transduced with both GM-CSF and IL-2 genes followed by an in vitro exposure to recombinant IFN-gamma, but survival was not prolonged. Tumorigenicity of mAML cells transduced with the gene coding for IFN-gamma was significantly reduced as manifested by prolonged survival of mice in comparison with animals inoculated with non-transduced mAML cells. Transduction by each of the aforementioned cytokines did not affect the immunogenicity of these tumor model cells. The results suggest that genetic modification of spontaneous and non-immunogenic experimental tumor models does not necessarily support direct utilization of cytokine gene therapy for clinical application. More effective methods have yet to be established in order to achieve an antitumor effect in spontaneous non-immunogenic malignancies.
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel 91120.
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Morecki
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Lubina-Salomon
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Slavin
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Nagler
D000818:Animals; D017690:Cell Transplantation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma