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细胞因子诱导的杀伤细胞在裸鼠异种移植模型中的抗肿瘤活性。

Antitumor activity of cytokine-induced killer cells in nude mouse xenograft model.

作者信息

Kim Hwan Mook, Kang Jong Soon, Lim Jaeseung, Kim Jee Youn, Kim Yeon Jin, Lee Soo Jae, Song Sukgil, Hong Jin Tae, Kim Youngsoo, Han Sang-Bae

机构信息

Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, 363-883, Korea.

出版信息

Arch Pharm Res. 2009 May;32(5):781-7. doi: 10.1007/s12272-009-1518-1. Epub 2009 May 27.

Abstract

Malignant glioma is the most common primary brain tumor in adults and the median survival for patients is less than a year. Despite aggressive treatments including surgical resection, radiotherapy, and chemotherapy, only modest improvement has been achieved in the survival of patients with glioma. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against human glioma cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 antibody-coated flasks for 5 days, followed by incubation in IL-2-containing medium for 9 days. The number of cells increased more than 200-fold and the viability was >90%. The resulting populations were consisted of 96% CD3(+), 2% CD3(-)CD56(+), 68% CD3(+)CD56(+), 2% CD4(+), <1% CD4(+)CD56(+), 80% CD8(+), and 49% CD8(+)CD56(+). This heterogeneous cell population was called as CIK cells. At an effector-target cell ratio of 30:1, CIK cells destroyed 43% of U-87 MG human glioma cells, as measured by the (51)Cr-release assay. In addition, CIK cells at doses of 0.3, 1, and 3 million cells per mouse inhibited 23%, 40%, and 50% of U-87 MG tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for glioma cancer patients.

摘要

恶性胶质瘤是成人中最常见的原发性脑肿瘤,患者的中位生存期不到一年。尽管采取了包括手术切除、放疗和化疗在内的积极治疗措施,但胶质瘤患者的生存期仅取得了适度改善。在本研究中,评估了细胞因子诱导的杀伤(CIK)细胞对人胶质瘤的体外和体内抗肿瘤活性。将人外周血单个核细胞在包被有抗CD3抗体的培养瓶中用含IL-2的培养基培养5天,然后在含IL-2的培养基中孵育9天。细胞数量增加了200多倍,存活率>90%。所得细胞群体由96%的CD3(+)、2%的CD3(-)CD56(+)、68%的CD3(+)CD56(+)、2%的CD4(+)、<1%的CD4(+)CD56(+)、80%的CD8(+)和49%的CD8(+)CD56(+)组成。这种异质性细胞群体被称为CIK细胞。通过(51)Cr释放试验测定,在效应细胞与靶细胞比例为30:1时,CIK细胞破坏了43%的U-87 MG人胶质瘤细胞。此外,在裸鼠异种移植试验中,每只小鼠分别给予0.3、1和3×1^6个细胞剂量的CIK细胞,分别抑制了U-87 MG肿瘤生长的23%、40%和50%。本研究表明,CIK细胞可能用作胶质瘤患者的过继性免疫治疗。

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