Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts.
Interleukin-21 (IL-21) is a novel cytokine that can induce proliferation of activated T cells and maturation of natural killer (NK) cells. We therefore examined whether expression of the IL-21 gene in tumor cells could generate antitumor responses. Murine colon carcinoma Colon 26 cells that were transduced with the mouse IL-21 gene (Colon 26/IL-21) were rejected in syngeneic mice and the mice subsequently acquired protective immunity. The growth of Colon 26/IL-21 tumors developed in nude mice was retarded compared with that of parent tumors, and this growth suppression was not observed in nude mice that were treated with anti-asialo GM(1) antibody. Spleen cells from the mice that had rejected Colon 26/IL-21 cells showed cytotoxic activity to Colon 26 but not to irrelevant tumor cells, and produced larger amounts of interferon-gamma upon stimulation with irradiated Colon 26 cells. Spleen cells from Colon 26/IL-21-tumor- but not parent-tumor-bearing mice had lytic activity to YAC-1 cells. These data suggest that expression of IL-21 in tumors induces T- and NK-cell-dependent antitumor effects.
Ugai
Shin-ichi
S
Department of Pathology, Chiba Cancer Centre Research Institute, Japan.
Shimozato
Osamu
O
Kawamura
Kiyoko
K
Wang
Yan-Qing
YQ
Yamaguchi
Taketo
T
Saisho
Hiromitsu
H
Sakiyama
Shigeru
S
Tagawa
Masatoshi
M
D000818:Animals; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012190:Retroviridae / Q000235:genetics; D000098546:Interleukin-21
D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21