IR@PKUHSC  > 北京大学第九临床医学院
学科主题临床医学
Programmed Death Receptor 1 (PD1) Knockout and Human Telomerase Reverse Transcriptase (hTERT) Transduction Can Enhance Persistence and Antitumor Efficacy of Cytokine-Induced Killer Cells Against Hepatocellular Carcinoma
Huang, Kanghua1; Sun, Bowen2; Luo, Nan3; Guo, Huahu3; Hu, Jili1,3; Peng, Jirun1,3
通讯作者Peng, Jirun(1,3)
关键词Carcinoma, Hepatocellular Cytokine-Induced Killer Cells Programmed Cell Death 1 Receptor Telomerase
刊名MEDICAL SCIENCE MONITOR
2018-07-03
DOI10.12659/MSM.910903
24页:4573-4582
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]T-CELLS ; PD-1 DISRUPTION ; MESSENGER-RNA ; IMMUNOTHERAPY ; EXPRESSION ; DELIVERY ; EXTENDS ; TUMORS
英文摘要

Background: The weak antitumor efficacy and limited lifespan are the main obstacles that hinder the therapeutic effect of cytokine-induced killer (CIK) cell immunotherapy. In the study, we enhanced the persistence and the antitumor efficacy of CIK cell through PD-1 knockout and hTERT transduction.

Material/Methods: CIK cells were cultured from patients with hepatocellular carcinoma and PD-1 gene was knocked out through the Cas9 ribonucleoproteins (Cas9 RNPs) electroporation. TIDE assay, T7E1 mismatch cleavage assay, and clone Sanger sequencing were used to detect PD-1 knockout efficiency. The immunophenotype was analyzed by flow cytometry. After PD-1 knockout, the hTERT gene was transduced into PD-1 KO/CIK cells with lentiviral transduction. The hTERT expression and persistence of hTERT/PD-1 KO/CIK cells were evaluated by Western blotting and proliferation curve. The antitumor efficacy was detected by ELISPOT and cytotoxicity assay. The telomere length was measured by the Q-FISH and qPCR method. The karyotype assay was used to analyze the chromosome structural stability.

Results: The optimal knockout efficiency of PD-1 gene in CIK cells could reach 41.23 +/- 0.52%. PD-1 knockout did not af- fect the immunophenotype of CIK cells. The hTERT transduction enhanced persistence and increased the telomere length. ELISPOT and cytotoxicity assay showed hTERT/PD-1 KO/CIK cells had an enhanced antitumor efficacy. Meanwhile, PD-1 KO/CIK cells transduced with hTERT showed a normal karyotype.

Conclusions: PD-1 knockout combined with hTERT transduction could prolong the lifespan and enhance antitumor efficacy of CIK cells against hepatocellular carcinoma cell line.

语种英语
WOS记录号WOS:000437377200001
通讯作者邮箱pengjr@medmail.com.cn
第一作者单位Capital Med Univ, Beijing Shijitan Hosp, Dept Surg, Beijing, Peoples R China
通讯作者单位Capital Med Univ, Beijing Shijitan Hosp, Dept Surg, Beijing, Peoples R China ; Peking Univ, Sch Clin Med 9, Dept Surg, Beijing, Peoples R China
ISSN1643-3750
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/142294
专题北京大学第九临床医学院
作者单位1.Beijing Sinovaccine Biotechnol Co Ltd, Beijing, Peoples R China;
2.Capital Med Univ, Beijing Shijitan Hosp, Dept Surg, Beijing, Peoples R China;
3.Peking Univ, Sch Clin Med 9, Dept Surg, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Huang, Kanghua,Sun, Bowen,Luo, Nan,et al. Programmed Death Receptor 1 (PD1) Knockout and Human Telomerase Reverse Transcriptase (hTERT) Transduction Can Enhance Persistence and Antitumor Efficacy of Cytokine-Induced Killer Cells Against Hepatocellular Carcinoma[J]. MEDICAL SCIENCE MONITOR,2018,24:4573-4582.
APA Huang, Kanghua,Sun, Bowen,Luo, Nan,Guo, Huahu,Hu, Jili,&Peng, Jirun.(2018).Programmed Death Receptor 1 (PD1) Knockout and Human Telomerase Reverse Transcriptase (hTERT) Transduction Can Enhance Persistence and Antitumor Efficacy of Cytokine-Induced Killer Cells Against Hepatocellular Carcinoma.MEDICAL SCIENCE MONITOR,24,4573-4582.
MLA Huang, Kanghua,et al."Programmed Death Receptor 1 (PD1) Knockout and Human Telomerase Reverse Transcriptase (hTERT) Transduction Can Enhance Persistence and Antitumor Efficacy of Cytokine-Induced Killer Cells Against Hepatocellular Carcinoma".MEDICAL SCIENCE MONITOR 24(2018):4573-4582.
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