CH-296和IFN-γ共同培养的CIK细胞治疗晚期恶性实体瘤临床观察

周莉; 于津浦; 李慧; 于文文; 任宝柱; 曹水; 任秀宝

doi:10.3969/j.issn.1000-8179.2013.03.010

CH-296和IFN-γ共同培养的CIK细胞治疗晚期恶性实体瘤临床观察

Clinical observation of CH-296 and IFN-γ in cytokine-induced killer cells in patients with advanced malignant solid tumors

摘要

摘要:
目的 CIK细胞具有异质性的抗肿瘤作用, 其中IFN-γ在增强CD3⁺CD56⁺细胞作用中起到关键作用。在TCR刺激信号存在的情况下, CH-296被发现能够刺激T细胞的增殖。本研究探讨CH-296和IFN-γ是否有相互促进CIK细胞表达的作用。
方法 CIK细胞在CH-296包被培养板或不包括的IFN-γ中培养14 d。将CIK细胞增殖、代谢、表型、细胞毒性同传统的CIK细胞相比较。20例(其中18例为Ⅳ期)患者接受了3个周期的RN-CIKs治疗。临床反应通过KPS评分和CT检查进行评价。
结果 CH-296通过减缓代谢和提高增殖以时间依赖的方式促进CIK细胞的表达。CH-296和IFN-γ共同培养带有T细胞表型的CIK细胞, 有更强的细胞毒性和细胞因子分泌功能。临床试验中未发生不良事件。16例患者临床症状有所缓解。总体临床反应率(PR+SD)为65%(13/20), 中位OS(16.95±6.10)个月。
结论 CH-296能够促进IFN-γ提高CIK细胞的抗肿瘤作用, 使CIK细胞有更强的增殖能力, 细胞毒作用并减缓代谢。

Abstract:
Objective Cytokine-induced killers(CIKs) are heterogenous antitumor effectors.Interferon gamma(IFN-γ) plays a pivotal role in amplifying the expression of CD3⁺CD56⁺ effectors.CH-296, a recombinant human fibronectin, has been demonstrated to stimulate T cell proliferation in the presence of TCR stimulating signals.This study aimed to determine whether CH-296 and IFN-γ had a synergistic effect on the cell proliferation of CIKs.
Methods CIKs were cultured in a cell culture medium/bag in the presence of immobilized CH-296 with retro-nectin CIKs(RN-CIKs) or without IFN-γ(RN-CIKs/del) for 14 days.The proliferation, apoptosis, phenotype, and cytotoxicity of these cells were compared with conventional CIKs.A total of 20 patients(18 of whom had stage Ⅳ tumors) received three cycles of RN-CIK treatment.The clinical responses were evaluated by KPS and CT scanning.
Results CH-296 promoted the expression of CIKs in a time-dependent manner by inhibiting apoptosis and increasing proliferation.Co-stimulation of CH-296 with IFN-γ amplified the stronger antitumor effectors with activated T cell phenotype that displayed potent cytotoxicity and increased secretion of cytokines upon antigen priming.No severe adverse event was observed in the trials.Sixteen patients experienced remission of clinical symptoms.The overall clinical response rate(partial remission and stable disease) was 65%(13/20), and the median overall survival rate was 16.95 ± 6.10 months.
Conclusion CH-296 had a synergistic effect with IFN-γ in promoting the antitumor efficiency of CIKs by increasing proliferation, inhibiting apoptosis, and enhancing cytotoxicity.

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