Anti-tumor effects of a tumor cell vaccine expressing a membrane-bound form of the IL-12 p35 subunit

被引:5
|
作者
Lim, Ho Yong [1 ]
Ju, Hee Young [2 ]
Chung, Hee-Yong [3 ]
Kim, Young Sang [1 ]
机构
[1] Chungnam Natl Univ, Dept Biochem, Coll Nat Sci, Taejon, South Korea
[2] Daejeon Sci High Sch, Taejon, South Korea
[3] Hanyang Univ, Dept Microbiol, Coll Med, Seoul 133791, South Korea
关键词
IL-12; p35; subunit; p40; membrane-bound form; cytotoxic T lymphocytes; anti-tumor immunity; direct priming; IFN gamma; CD69; STIMULATORY FACTOR INTERLEUKIN-12; T RESPONSES INVITRO; P40; HOMODIMER; RECOMBINANT INTERLEUKIN-2; HETERODIMERIC CYTOKINE; GAMMA PRODUCTION; TNF-ALPHA; IMMUNITY; MACROPHAGES; INHIBITION;
D O I
10.4161/cbt.10.4.12310
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated whether expression of the IL-12 p35 subunit in membrane-bound form in tumor cells enhanced their immunogenicity. Since p35 is only secreted when associated with the IL-12 p40 subunit, we generated tumor cells expressing membrane-bound forms of p35 and p40 as chimeras with the transmembrane/cytoplasmic region of TNF alpha (mbIL-12p35 and mbIL-12p40). The relevant vectors were transfected into MethA fibrosarcoma cells, and mbIL-12p35 or mbIL-12p40-expressing tumor clones were isolated and their ability to induce anti-tumor immunity studied. Cells of the mbIL-12p35 tumor clone induced CD69 expression and IFN gamma production in purified CD8(+) T cells in vitro, and their in vivo tumorigenicity was reduced. Cells of the mbIL-12p40 tumor clone failed to show either of these activities. Mice that had rejected cells of the mbIL-12p35 tumor clone possessed systemic anti-tumor immunity to wild type tumor cells. The growth rate of mbIL-12p35 tumor cells was greater in CD8(+) T cell-depleted mice than in CD4(+) T cell- and NK cell-depleted mice or normal mice, suggesting that CD8(+) T cells were mainly responsible for the anti-tumor immunity. These results indicate that expression of mbIL-12p35 on tumor cells enhances their immunogenicity by increasing their ability to activate CD8(+) T cells, possibly by direct priming.
引用
收藏
页码:336 / 343
页数:8
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