Involvement of T-cell subsets and natural killer (NK) cells in the growth suppression of murine fibrosarcoma cells transfected with interleukin-12 (IL-12) genes

✍ Scribed by Michael Schmitt; Hiroaki Ikeda; Yasuhiko Nagata; Xiaogang Gu; Lijie Wang; Kagemasa Kuribayashi; Hiroshi Shiku

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 198 KB
• Volume: 72
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970729)72:3<505::aid-ijc20>3.0.co;2-9

✦ Synopsis

A 3-methylcholanthrene-induced fibrosarcoma cell line of BALB/c origin, CMS5j, was co-transfected with cDNA for the p40 and p35 subunits of interleukin-12 (IL-12). Injection of transfected cells producing 5 3 10 3 U IL-12/10 6 cells/ml/day in nude mice with an established fibrosarcoma at a contralateral site efficiently eliminated tumor growth in the early phase (injection on day 0 or 4) but not later (day 8). This effect could be abrogated by simultaneous i.v. injection of antibodies against NK1.1 or ASGM1 (asialoGM1 5 ganglio-N-tetraosyl-ceramide), which indicates that natural killer (NK) cells play a major role in tumor eradication or suppression when stimulated by IL-12. In wild-type mice, application of IL-12secreting CMS5j cells abrogated growth of tumors established 8 days before but not earlier. Based on our experiments with antibody blocking in vivo, all CD4 1 , CD8 1 and ASGM1 1 cells are involved in tumor rejection. However, in our system, CD4 1 cells or CD8 1 cells alone, but not ASGM1 1 cells alone, also could lead to tumor rejection. IL-12engineered fibrosarcoma cells may constitute an efficient and safe system for immunotherapy of cancer. Int.