분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2017-02-24 03:47:12 , Hit : 1288
 CRISPR Turbocharges CAR T Cells, Boosts Cancer Immunotherapy

GEN News Highlights
More »
February 23, 2017

http://www.genengnews.com/gen-news-highlights/crispr-turbocharges-car-t-cells-boosts-cancer-immunotherapy/81253925?utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=01&utm_campaign=GEN+Daily+News+Highlights_20170223


In a model of acute lymphoblastic leukemia, CAR T cells created with CRISPR outperformed those made with technology that relies on randomly integrating vectors.

When T cells are modified to fight cancer more effectively, cellular mechanics don’t pick up a socket wrench. Instead, they take hold of retroviral or lentiviral technology, which is used to install genes for synthetic T-cell receptors. Such technology, however, doesn’t always place genes in just the right place. Enter Mr. GoodCRISPR. This mechanic uses CRISPR gene-editing technology, which is more precise.

CRISPR can be used to install genes, such as chimeric antigen receptor (CAR) genes, into specific parts of the genome. Presumably, when CRISPR is used to build CAR T cells, their genomic engines will run more smoothly—and rack up more trouble-free miles. Such endurance is important for CAR T cells, which are being used in immunotherapy applications. These are long-distance races, and they are particularly grueling when CAR T cells must outpace cancer.

A road test of sorts has been staged by scientists based at Memorial Sloan Kettering Cancer Center (MSK). They decided that CRISPR T-cell engineering might be more effective than conventional T-cell engineering, which, the scientists have observed, can result in clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing.

The scientists built CRISPR-engineered CAR T cells and evaluated their efficacy in a model of acute lymphoblastic leukemia. The results of this work appeared February 22 in Nature, in an article entitled, “Targeting a CAR to the TRAC Locus with CRISPR/Cas9 Enhances Tumour Rejection.” As the title suggests, the MSK team took advantage of CRISPR’s ability to deliver genes to selected genomic loci.

“Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia,” wrote the article’s authors. “We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion.”

Essentially, the MSK team showed that CRISPR technology can deliver a CAR gene to a very specific location in the genome of the T cell. Moreover, the team demonstrated that this precise approach resulted in CAR T cells that had more stamina.

The CRISPR-modified T cells are able to kill tumor cells for longer because they are less prone to exhaustion. More robust T cells could eventually lead to safer, more effective use of cell-based immunotherapy in patients.

"Cancer cells are relentless in their attempt to evade treatment, so we need CAR T cells that can match and outlast them," explained Michel Sadelain, M.D., Ph.D., senior author on the Nature paper and director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at MSK. "This new discovery shows that we may be able to harness the power of genome editing to give these 'living therapies' a built-in boost. We are eager to continue exploring how genome-editing technology could give us the next generation of CAR T cell therapy."

Some of the first clinical trials using CRISPR technology are currently in the planning stages. Dr. Sadelain and his team aim to eventually explore the safety and efficacy of these CRISPR-built CAR T cells in a trial.







1167   Scientists unveil CRISPR-based diagnostic platform  이성욱 2017/04/14 811
1166   [사이언스 카페] 美 FDA, 민간업체의 '개인용 유전자 검사' 첫 허용  이성욱 2017/04/10 794
1165   암 전이에 핵심 역할하는 줄기세포 찾았다  이성욱 2017/04/03 1161
1164   ‘단세포 인공생명체’ 눈앞에 성큼  이성욱 2017/03/11 792
1163   Beyond CRISPR Cuts: Five Complements To Cas9  이성욱 2017/02/24 984
1162   Smallest CRISPR So Far Comes from Food Poisoning Bacteria  이성욱 2017/02/24 922
  CRISPR Turbocharges CAR T Cells, Boosts Cancer Immunotherapy  이성욱 2017/02/24 1288
1160   [바이오토픽] 브로드 연구소, 열띤 CRISPR 특허전쟁에서 승리  이성욱 2017/02/16 1056
1159   Judges Side with Broad Institute in CRISPR Patent Dispute  이성욱 2017/02/16 952
1158   미국 과학·공학·의학 아카데미, 「GM 베이비」의 진행방향에 대한 윤곽 발표  이성욱 2017/02/16 1068
1157   Nano-CRISPR Packages Attain 90% Delivery Rate with Engineered Cas9  이성욱 2017/02/09 1325
1156   유전자 치료로 청력 되살린다  이성욱 2017/02/08 1347
1155   바이러스들도 서로 소통..“상황에 따라 감염방식 결정”  이성욱 2017/01/24 1130
1154   Oligonucleotide Therapeutics Near Approval  이성욱 2017/01/10 1165
1153   Off Switch Found for Common Version of the CRISPR-Cas9 System  이성욱 2017/01/02 992
1152   Editas Expands CRISPR Capabilities through New Technology Licensing  이성욱 2016/12/22 817
1151   RNA Modification Helps Drosophila Straighten Up and Fly Right  이성욱 2016/12/10 885
1150   Anti-CRISPR Protein Is Gene Editing “Off-Switch”  이성욱 2016/12/10 1889
1149   Could Gene Therapy Work for Alzheimer’s Disease?  이성욱 2016/10/12 1156
1148   EU, 2번째 유전자치료제 ‘스트림벨리스’ 승인  이성욱 2016/09/05 1144

[1][2][3][4][5] 6 [7][8][9][10]..[64] [다음 10개]
 

Copyright 1999-2021 Zeroboard / skin by ROBIN