期刊
TRENDS IN BIOTECHNOLOGY
卷 40, 期 7, 页码 875-890出版社
CELL PRESS
DOI: 10.1016/j.tibtech.2021.12.009
关键词
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资金
- American Foundation for Pharmaceutical Education (AFPE)
- ALSAM Foundation
- Huntsman Cancer Institute (HCI)
- National Comprehensive Cancer Network (NCCN)
The use of chimeric antigen receptor (CAR) T cells has revolutionized cancer treatment, however, the high affinity of most CAR-binding domains leads to excessive T-cell activation. Recent studies have explored the use of low-affinity CAR-binding domains and evaluated technologies to engineer and screen low-affinity antibody variants for CAR T-cell development, aiming to streamline the development of more functional and selective therapeutics.
Chimeric antigen receptor (CAR) T cells have revolutionized cancer treatment. CARs use antibody-derived binding domains to redirect T cells to antigens expressed on the surface of cancer cells. However, the high affinity of most currently used CAR-binding domains results in excessive T-cell activation limiting CAR T-cell persistence and the inability to differentiate between antigen-high tumor cells and antigen-low healthy cells. We review recent data on the use of low-affinity CAR-binding domains and evaluate technologies and approaches to engineer and screen low-affinity antibody variants for CAR T-cell development. We propose an ideal workflow for the generation of optimal low-affinity binders derived from existing antibodies to streamline the development of more functional and selective therapeutics.
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