Preliminary study on mouse interleukin-21 application in tumor gene therapy.
Interleukin-21 (IL-21) is a recently characterized T cell-derived cytokine with a significant homology to IL-2, IL-4 and IL-15. To determine whether IL-21 has broad immunoregulatory activity and can stimulate durable antitumour responses, we constructed mouse IL-21 (mIL-21) recombinant plasmid and evaluated its antitumor efficacy. Mouse IL-21 cDNA was amplified from Con A-activated mouse T cells by RT-PCR. Recombinant pcDNA3.1/mIL-21 was constructed and transfected into Sp2/0 cells. Mouse IL-21 expression was analyzed by Western blotting and its activities were detected by 3H-TdR incorporation and MTT assay. The recombinant pcDNA3.1/mIL-21 was injected s.c. into tumor lump. Tumor size, weight, the activities of CTLs, NK cells and LAK cells and serum IFN-gamma level were measured for evaluating mIL-21 mediated antitumor responses. The results indicated that mIL-21 was correctly expressed in Sp2/0 cells and it can improve the proliferation of T cells and B cells, and enhance NK cytotoxic activity in vitro. The activities of CTL and NK cells, and serum IFN-gamma level were significantly improved, furthermore the tumor growth was obviously suppressed in pcDNA3.1/mIL-21 treated mice. However, the LAK activity did not alter significantly. Taken together, this study suggests that the injection with recombinant plasmid containing mIL-21 is a potential approach for tumor gene therapy.
Dou
Jun
J
Department of Microbiology and Immunology, Basic Medical School, Southeast University, Nanjing 210009, China. njdoujun@yahoo.com.cn
Chen
Guobin
G
Wang
Jing
J
Zhao
Fengshu
F
Chen
Junsong
J
Fang
Xuesong
X
Tang
Quan
Q
Chu
Lili
L
D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D007267:Injections; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D023041:Xenograft Model Antitumor Assays; D000098546:Interleukin-21
D007378:Interleukins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000098546:Interleukin-21