Proc Annu Meet Am Assoc Cancer Res; 38:A811 1997. Unique Identifier : AIDSLINE ICDB/98637811 Sugg SL; Lange J; Fraker DL; Department of Surgery, University of Toronto, Ontario, Canada
Abstract:
Introduction: The early region 1A (E1A) of adenovirus type 2 and 5 (Ad 2,5) was recently found to have tumor suppressive functions. We investigated the hypothesis that suppressed tumorigenicity of E1A transfected murine fibrosarcoma cells is immunologically mediated. Methods: Murine fibrosarcoma cell line 102.4 was transfected with a eukaryotic expression vector containing the Ad 2 E1A gene. E1A expression was determined by FACS and western blot analysis using E1A Ab-1 (Oncogene Science). C57Bl6, athymic nude, and C57Bl6-BG (NK deficient) mice were injected subcutaneously with tumor cells and measured. C57Bl6 mice were subjected to irradiation (500 cG) or in vivo CD-4 or CD-8 depletion with rat monoclonal antibodies. Results: Vector control (vec) and 3 E1A expressing clones, A3, B1, and C1, were used in animal experiments. In immunocompetent, NK deficient and CD-4 depleted mice, vec grew but A3 and C1 regressed completely by day 15. A3 and C1 did not regress in irradiated, nude, or CD-8 depleted mice. E1A expression was still present. B1 did not regress in immunocompetent mice. Conclusion: Ad2 E1A expression in murine fibrosarcoma results in tumor regression in 2 of 3 clones. The regression is mediated by CD-8 T-cells and not by CD-4 or NK cells. The tumor suppressor gene functions of E1A may be augmented by a specific immunological response in vivo.
Keywords: Adenovirus E1A Proteins/*GENETICS Animal CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Fibrosarcoma/*GENETICS/*IMMUNOLOGY Killer Cells, Natural/IMMUNOLOGY Lymphocyte Depletion Mice Mice, Inbred C57BL *Transfection ABSTRACT 980228
M9820766
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