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
Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, 363-883, Korea.
Arch Pharm Res. 2009 May;32(5):781-7. doi: 10.1007/s12272-009-1518-1. Epub 2009 May 27.
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.
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。