T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies

Fanlin Li, Huihui Zhang, Wanting Wang, Puyuan Yang, Yue Huang, Junshi Zhang, Yaping Yan, Yuan Wang, Xizhong Ding, Jie Liang, Xinyue Qi, Min Li, Ping Han, Xiaoqing Zhang, Xin Wang, Jiang Cao, Yang-Xin Fu and Xuanming Yang ()
Additional contact information
Fanlin Li: Shanghai Jiao Tong University
Huihui Zhang: Shanghai Jiao Tong University
Wanting Wang: Shanghai Jiao Tong University
Puyuan Yang: Shanghai Jiao Tong University
Yue Huang: Shanghai Jiao Tong University
Junshi Zhang: Shanghai Jiao Tong University
Yaping Yan: Shanghai Jiao Tong University
Yuan Wang: Shanghai Jiao Tong University
Xizhong Ding: Shanghai Jiao Tong University
Jie Liang: Shanghai Jiao Tong University
Xinyue Qi: Shanghai Jiao Tong University
Min Li: Shanghai Jiao Tong University
Ping Han: Shanghai Jiao Tong University
Xiaoqing Zhang: Shanghai Jiao Tong University
Xin Wang: Shanghai Longyao Biotechnology Limited
Jiang Cao: Affiliated Hospital of Xuzhou Medical University
Yang-Xin Fu: University of Texas Southwestern Medical Center
Xuanming Yang: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune suppression arising from bystander T cell aplasia. Here, we show the selective killing of malignant T cells without affecting normal T cell-mediated immune responses in vitro and in a mouse model of disseminated leukemia. Further, we develop a CAR construct that carries the single chain variable fragment of a subtype-specific antibody against the variable TCR β-chain region. We demonstrate that these anti-Vβ8 CAR-T cells are able to recognize and kill all Vβ8+ malignant T cells that arise from clonal expansion while sparing malignant or healthy Vβ8− T cells, allowing sufficient T cell-mediated cellular immunity. In summary, we present a proof of concept for a selective CAR-T cell therapy to eradicate T cell malignancies while maintaining functional adaptive immunity, which opens the possibility for clinical development.

Date: 2022
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32092-8 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:13:y:2022:i:1:d:10.1038_s41467-022-32092-8

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

DOI: 10.1038/s41467-022-32092-8

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 ().