自体CIK细胞联合化疗治疗恶性黑色素瘤的临床观察

发布时间：2018-05-14 23:11

本文选题：细胞因子诱导的杀伤细胞 + 恶性黑色素瘤　；参考：《苏州大学》2012年硕士论文

【摘要】：目的体外培养获得细胞因子诱导的杀伤细胞（CIK细胞），研究其表型与生物学活性，并探讨分析自体CIK细胞联合化疗治疗恶性黑色素瘤术后患者的临床意义。方法利用Ficoll分离液从外周血中分离单个核淋巴细胞，通过INF-γ、rhIL-2、rhIL-1α、anti-CD3McAb诱导培养，获得大量CIK细胞。流式细胞分析法对CIK细胞进行动态表型分析；MTT法检测不同阶段CIK细胞的杀伤活性。对37例恶性黑色素瘤术后行六周期化疗的患者进行回顾性分析研究，其中12例患者化疗结束后接受CIK细胞回输治疗，25例单纯化疗，化疗均采用CVD方案：顺铂20mg/m~2D1-5，长春碱1.6mg/m~2D1-5，氮烯咪胺800mg/m~2D1。对自体CIK细胞治疗前后患者外周血T细胞亚群检测结果进行随访观察，并应用log-rank检验对两组中位生存期及中位无进展生存期进行比较。结果①CIK细胞体外显著扩增，培养第14天至21天期间形成高峰平台，CIK细胞对K562及Raji细胞的细胞毒活性在14天时达峰值，分别为（76.65±16.78）%与（75.32±15.61）%。②CIK联合化疗组患者外周血NK、CIK（CD3~+CD56~+）、CD3~+与CD4~+细胞百分比以及CD4~+/CD8~+比值明显升高，CD8~+细胞比例下降；而单纯化疗组上述指标没有显著变化。③CIK联合化疗组与单纯化疗组患者的中位总生存期分别为66个月（95%CI：47.04~85.09月）与45个月（95%CI：）a，差异无统计学意义(χ~2=1.710，P=0.191)；两组中位无进展生存期分别为33个月（95%CI：18.830~48.570月）与17个月（95%CI：8.441~26.22月），差异有统计学意义(χ~2=6.768，P=0.009)。结论培养至第14天CIK细胞增殖与杀伤活性均达到峰值，适合应用于治疗。采用自体CIK细胞治疗恶性黑色素瘤术后患者可以促进化疗后免疫功能的恢复，，延长无进展生存期。
[Abstract]:Objective to study the phenotype and biological activity of cytokine induced killer cells in vitro and to explore the clinical significance of autologous CIK cells combined with chemotherapy in the treatment of malignant melanoma. Methods Mononuclear lymphocytes were isolated from peripheral blood by Ficoll isolate, and a large number of CIK cells were obtained by induction and culture with INF- 纬 -rhIL-2rhIL-1 伪 anti-CD3 McAb. The dynamic phenotypic analysis of CIK cells by flow cytometry was used to detect the cytotoxicity of CIK cells at different stages. A retrospective study was conducted on 37 patients with malignant melanoma who received six cycles of chemotherapy after operation. Among them, 12 patients received CIK cell therapy after chemotherapy and 25 received chemotherapy alone. Chemotherapy was performed with CVD regimen: cisplatin 20 mg / mt2D1-5, vincristine 1.6 mg / mt2D1-5, azomidine 800 mg / mD1. The T cell subsets in peripheral blood of patients with autologous CIK cells before and after treatment were followed up, and the median survival time and median progression-free survival time were compared by log-rank test. Results 1CIK cells proliferated significantly in vitro, and the cytotoxic activity of 1CIK cells against K562 and Raji cells reached the peak at 14 days from day 14 to day 21. In the combination chemotherapy group of 76.65 卤16.78% and 75.32 卤15.61)%.2CIK respectively, the percentage of CD3- CD56 ~ + CD3- and CD4- cells and the ratio of CD4- / CD8- were significantly increased and the percentage of CD8- cells decreased. The median total survival time of patients in CIK combined chemotherapy group and simple chemotherapy group was 66 months, 95 CI: 47.04 ~ 85.09 months, respectively. There was no significant difference between the two groups (蠂 2 + 1.710 P 0.191) and 45 months respectively (蠂 2 + 1.710 P 0.191), the median survival time of the patients in the combination chemotherapy group and simple chemotherapy group was 66 months ~ 95 CI: 47.04 ~ 85.09 months respectively, and there was no significant difference between the two groups (蠂 ~ 2 + 1.710 P 0.191). There were significant differences between the retention period of 95% (18.830 ~ 48.570 months) and 95% (8.441 ~ 26.22 months) of 17 months (蠂 ~ (2 / 2) 6.768 / P ~ (0.009). Conclusion the proliferation and cytotoxicity of CIK cells reached the peak on the 14th day of culture, which is suitable for treatment. Using autologous CIK cells to treat malignant melanoma patients after operation can promote the recovery of immune function after chemotherapy and prolong the progression-free survival.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R739.5

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