Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies

Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies

Abstract Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and...

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Bibliographic Details
Main Authors: Chaoting Zhang, Heyilimu Palashati, Zhuona Rong, Ningjing Lin, Luyan Shen, Ying Liu, Shance Li, Bentong Yu, Wenjun Yang, Zheming Lu
Format: Article
Language:English
Published: BMC 2020-11-01
Series:Molecular Cancer
Subjects:
T cell receptor β-chain constant region 1
CAR-T
T-cell malignancy
Online Access:http://link.springer.com/article/10.1186/s12943-020-01282-7
Description
Summary:Abstract Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing.
ISSN:1476-4598

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