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

• Published in: International journal of cancer 1997-07, Vol.72 (3), p.505-511
• Main Authors: Schmitt, Michael, Ikeda, Hiroaki, Nagata, Yasuhiko, Gu, Xiaogang, Wang, Lijie, Kuribayashi, Kagemasa, Shiku, Hiroshi
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - pharmacology; Biological and medical sciences; Cell Division; Female; Fibrosarcoma - chemically induced; Fibrosarcoma - immunology; Fibrosarcoma - pathology; G(M1) Ganglioside - immunology; Immunization, Passive; Interleukin-12 - genetics; Interleukin-12 - physiology; Killer Cells, Natural - immunology; Medical sciences; Methylcholanthrene; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Other treatments; T-Lymphocyte Subsets - immunology; Transfection; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970729)72:3<505::AID-IJC20>3.0.CO;2-9

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 × 103 U IL‐12/106 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 = 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‐12‐secreting CMS5j cells abrogated growth of tumors established 8 days before but not earlier. Based on our experiments with antibody blocking in vivo, all CD4+, CD8+ and ASGM1+ cells are involved in tumor rejection. However, in our system, CD4+ cells or CD8+ cells alone, but not ASGM1+ cells alone, also could lead to tumor rejection. IL‐12‐engineered fibrosarcoma cells may constitute an efficient and safe system for immunotherapy of cancer. Int. J. Cancer 72:505–511, 1997. © 1997 Wiley‐Liss, Inc.