气候变化领域集成服务门户(CCPortal): CRISPR-engineered T cells in patients with refractory cancer

CCPortal

DOI	10.1126/science.aba7365
	CRISPR-engineered T cells in patients with refractory cancer
	Stadtmauer E.A.; Fraietta J.A.; Davis M.M.; Cohen A.D.; Weber K.L.; Lancaster E.; Mangan P.A.; Kulikovskaya I.; Gupta M.; Chen F.; Tian L.; Gonzalez V.E.; Xu J.; Jung I.-Y.; Joseph Melenhorst J.; Plesa G.; Shea J.; Matlawski T.; Cervini A.; Gaymon A.L.; Desjardins S.; Lamontagne A.; Salas-Mckee J.; Fesnak A.; Siegel D.L.; Levine B.L.; Jadlowsky J.K.; Young R.M.; Chew A.; Hwang W.-T.; Hexner E.O.; Carreno B.M.; Nobles C.L.; Bushman F.D.; Parker K.R.; Qi Y.; Satpathy A.T.; Chang H.Y.; Zhao Y.; Lacey S.F.; June C.H.
发表日期	2020
ISSN	0036-8075
卷号	367 期号:6481
英文摘要	CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells to fight cancer. We report a first-in-human phase 1 clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRa (TRAC) and TCRb (TRBC), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding programmed cell death protein 1 (PD-1; PDCD1), was performed to improve antitumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Although chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months, suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene editing for cancer immunotherapy. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
关键词	heterodimer programmed death 1 receptor T lymphocyte receptor alpha chain T lymphocyte receptor beta chain cancer cell gene gene expression genetic engineering immunity protein adult aged Article cancer patient cell engineering chromosome translocation clinical article clustered regularly interspaced short palindromic repeat controlled study CRISPR-CAS9 system feasibility study female gene editing gene expression gene frequency gene locus genetic code human human cell male middle aged myeloma PDCD1 gene phase 1 clinical trial priority journal sarcoma T lymphocyte TRAC gene TRBC gene tumor immunity
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133682
推荐引用方式 GB/T 7714	Stadtmauer E.A.,Fraietta J.A.,Davis M.M.,et al. CRISPR-engineered T cells in patients with refractory cancer[J]. Science,2020,367(6481).
APA	Stadtmauer E.A..,Fraietta J.A..,Davis M.M..,Cohen A.D..,Weber K.L..,...&June C.H..(2020).CRISPR-engineered T cells in patients with refractory cancer.,367(6481).
MLA	Stadtmauer E.A.,et al."CRISPR-engineered T cells in patients with refractory cancer".367.6481(2020).