Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming

Yao Wang, Chuan Tong, Hanren Dai, Zhiqiang Wu, Xiao Han, Yelei Guo, Deyun Chen, Jianshu Wei, Dongdong Ti, Zongzhi Liu, Qian Mei, Xiang Li, Liang Dong, Jing Nie, Yajing Zhang and Weidong Han ()
Additional contact information
Yao Wang: Chinese People’s Liberation Army General Hospital
Chuan Tong: Chinese People’s Liberation Army General Hospital
Hanren Dai: Chinese People’s Liberation Army General Hospital
Zhiqiang Wu: Chinese People’s Liberation Army General Hospital
Xiao Han: Chinese People’s Liberation Army General Hospital
Yelei Guo: Chinese People’s Liberation Army General Hospital
Deyun Chen: Chinese People’s Liberation Army General Hospital
Jianshu Wei: Chinese People’s Liberation Army General Hospital
Dongdong Ti: Chinese People’s Liberation Army General Hospital
Zongzhi Liu: Beijing Institute of Genomics, Chinese Academy of Sciences
Qian Mei: Chinese People’s Liberation Army General Hospital
Xiang Li: Chinese People’s Liberation Army General Hospital
Liang Dong: Chinese People’s Liberation Army General Hospital
Jing Nie: Chinese People’s Liberation Army General Hospital
Yajing Zhang: Chinese People’s Liberation Army General Hospital
Weidong Han: Chinese People’s Liberation Army General Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Insufficient eradication capacity and dysfunction are common occurrences in T cells that characterize cancer immunotherapy failure. De novo DNA methylation promotes T cell exhaustion, whereas methylation inhibition enhances T cell rejuvenation in vivo. Decitabine, a DNA methyltransferase inhibitor approved for clinical use, may provide a means of modifying exhaustion-associated DNA methylation programmes. Herein, anti-tumour activities, cytokine production, and proliferation are enhanced in decitabine-treated chimeric antigen receptor T (dCAR T) cells both in vitro and in vivo. Additionally, dCAR T cells can eradicate bulky tumours at a low-dose and establish effective recall responses upon tumour rechallenge. Antigen-expressing tumour cells trigger higher expression levels of memory-, proliferation- and cytokine production-associated genes in dCAR T cells. Tumour-infiltrating dCAR T cells retain a relatively high expression of memory-related genes and low expression of exhaustion-related genes in vivo. In vitro administration of decitabine may represent an option for the generation of CAR T cells with improved anti-tumour properties.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20696-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20696-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20696-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().