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.
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 x 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 = 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.
Schmitt
M
M
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Ikeda
H
H
Nagata
Y
Y
Gu
X
X
Wang
L
L
Kuribayashi
K
K
Shiku
H
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D005677:G(M1) Ganglioside / Q000276:immunology; D007116:Immunization, Passive; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018664:Interleukin-12; D005677:G(M1) Ganglioside; D008748:Methylcholanthrene; C018835:asialo GM1 ganglioside