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1、细胞过继免疫治疗肿瘤的临床研究进展,张叔人 中国医学科学院 北京协和医科大学 肿瘤研究所,细胞免疫治疗肿瘤的发展,上世纪80年代初，Steven A. Rosenberg, Chief of Surgery at the National Cancer Institute，NIH，USLAK+IL-2 22例中：CR1，PR8（41%）LAK、TIL、基因修饰、联合放、化疗,国内细胞免疫治疗研究热潮,80年代末90年代初LAK推动了国内细胞免疫治疗研究的热潮。LAK：自体、异体、胎儿脾、胸腺、脐血90年代，我国药品监督管理局制定了相应法规，并公布实施。此后又进行了多次修订。首例申报CIK，北京
2、人民医院（陆道培）DC疫苗，第二军医大学（曹雪涛）上个世纪末CIK、DC-CIK、NK、 gdT、TIL 、免疫杀手细胞等开展了多种免疫细胞抗肿瘤研究。,肿瘤的细胞免疫治疗 经过体外培养加工,细胞过继免疫治疗(adoptive immunotherapy)LAK、TIL、CIK、DC-CIK、NK、NKT、CTL 、 gdT自体/异体，基因修饰细胞瘤苗（tumor vaccine）肿瘤细胞树突状细胞 自体/异体、基因修饰融合细胞,CIK Cytokine induced killer,PBMC IFN-g anti-CD3, IL-2, IL-1a,2009，Germany，Prof. Dr.
3、 Schmidt-Wolf 建立了CIK临床研究登记网站 www.cik-info.org，目前收集发表的文章39篇，中国人发表26篇(占2/3)。 2011，J Cancer Res Clin Oncol. “Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC)”. PubMed the keywords CIK cells clinical trials，evaluated 11 studies（426人）. 并与作者联系核实 涉及的杂志：Digestive
4、and Liver Disease, Chinese Journal of Cancer, Anticancer Research, World Journal of Gastroenterology , Haematologica, British Journal of Cancer, Biology of Blood, and Marrow Transplantation. In some studies, abstracts were only available in Chinese. Unfortunately, these studies are often published o
5、nly in Chinese. international standard,CIK 临床研究国际登记网站,Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC),C. Hontscha Y. Borck H. Zhou D. Messmer I. G. H. Schmidt-Wolf J Cancer Res Clin Oncol (2011) 137:305310,入组标准 排除标准,Table 2. Indications and contraindicati
6、ons of CIK immunotherapy in 11 clinical trials,Table 1 Tumor entity with number of respective patients, male-to-female ratio, andtherapeutic effects,Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC),脊髓发育不良,Cytokine Induced Killer Cells as Promising Immunoth
7、erapy for Solid Tumors Dario Sangiolo, Italy Journal of Cancer 2011; 2: 363-36,CIK治疗实体瘤的9个临床研究报道,Fig. 1. Disease-free survival curves of the three groups. KaplanMeier was employed to estimate the disease-free survival rates of the three groups. Logrank test shows a significantly higher rates in the
8、CIK-I group (p = 0.001) and the CIK-II group (p = 0.004) than in the control group. No statistical significance was found between the CIK-I group and the CIK-II group (p = 0.345).,A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resec
9、tion of hepatocellular carcinoma（127例） Hui Dong, Qiang Li , Jian Wang, Ti Zhang, Da-Lu Kong, Digestive and Liver Disease 41 (2009) 3641 Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Tianjin, Peoples Republic of China,无病生存期 肝癌切除术后1个月开始治疗，CIK-I x3次 CIK-II x6次 对照,F
10、ig. 2 The 1-, 3- and 5-year disease-free survival rates in patients receiving CIK cells (groups 1 and 2) when compared to no CIK cell treatment (127 patients); (trial 11). Group 1 was treated with 3 courses of CIK cells, group 2 was treated with 6 courses of CIK cells and the control group (group 3)
11、 received no CIK cell treatment for comparison,1-, 3- 和 5-年无病生存率,A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma（127例）,A randomized, controlled trial of postoperative adjuvant cytokine-induced ki
12、ller cells immunotherapy after radical resection of hepatocellular carcinoma,1-, 3- and 5-year overall survival rates,生存期,Figure 1 Survival rates of patients after cytokine-induced killer cells immunotherapy plus chemotherapy and chemotherapy alone. CIK: Cytokineinduced killer.,CIK治疗胃癌频率与疗效 Increasi
13、ng the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients (156例) Jing-Ting Jiang, . Xue-Guang Zhang 苏州大学 World J Gastroenterol 2010 December 28; 16(48): 6155-6162,World J Gastroenterol 2010 December 28; 16(48): 6155-6162 Jing-Ting Jiang, Yue-Ping Shen
14、, Chang-Ping Wu, Yi-Bei Zhu, Wen-Xiang Wei, Lu-Jun Chen, Xiao Zheng,Jing Sun, Bin-Feng Lu, Xue-Guang Zhang 苏州大学,Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients,Cord blood-derived cytokine-induced killer cells biotherapy combined with
15、 second-line chemotherapy in the treatment of advanced solid malignancies (40例),Qi Niu, et.al., International Immunopharmacology 11 (2011) 449456 Beijing GreatWall International Cancer Center, No. 309 PLA Hospital, Beijing, PR China,中位生存期 化疗 7.52个月 化疗+CIK 11.17个月 差3.65个月,化疗联合脐血CIK治疗恶性肿瘤,Cord blood-d
16、erived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies,中国肺癌杂志 2009, Vol.12, No. 9 昆明医学院第三附属医院 赵光强 黄云超 叶联华 段林灿 周永春 杨凯云 马千里 雷玉洁 宋鑫 黄明 杨银山,全身化疗和支气管动脉灌注联合CIK过继免疫 治疗期非小细胞肺癌的临床研究（113例）,3 CR, 1 PR, 6 SD，6PD / 16 CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS25% 62.5% Volume 25, Number 4, 2010,
