Tuning the ignition of CAR: optimizing the affinity of scFv to improve CAR-T therapy

How single-chain variable fragments (scFvs) affect the functions of chimeric antigen receptors (CARs) has not been well studied. Here, the components of CAR with an emphasis on scFv were described, and then several methods to measure scFv affinity were discussed. Next, scFv optimization studies for...

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Bibliographic Details
Published inCellular and molecular life sciences : CMLS Vol. 79; no. 1; p. 14
Main Authors Duan, Yanting, Chen, Ruoqi, Huang, Yanjie, Meng, Xianhui, Chen, Jiangqing, Liao, Chan, Tang, Yongmin, Zhou, Chun, Gao, Xiaofei, Sun, Jie
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.01.2022
Springer Nature B.V
Subjects
Affinity
Animal models
Animals
Antigens
Automobiles
Biochemistry
Biomedical and Life Sciences
Biomedicine
CD19 antigen
CD38 antigen
Cell Biology
Chimeric antigen receptors
Disease Models, Animal
ErbB-2 protein
Humans
Immunotherapy, Adoptive
Life Sciences
Neoplasms - immunology
Neoplasms - therapy
Optimization
Receptors
Receptors, Chimeric Antigen - chemistry
Receptors, Chimeric Antigen - metabolism
Review
Single-Chain Antibodies - chemistry
Single-Chain Antibodies - metabolism
Synthetic Biology
Toxicity
Tumors
Tuning
Affinity
Chimeric antigen receptor
Adoptive cell therapy
scFv
On-target/off-tumor
Immunotherapy
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Summary:How single-chain variable fragments (scFvs) affect the functions of chimeric antigen receptors (CARs) has not been well studied. Here, the components of CAR with an emphasis on scFv were described, and then several methods to measure scFv affinity were discussed. Next, scFv optimization studies for CD19, CD38, HER2, GD2 or EGFR were overviewed, showing that tuning the affinity of scFv could alleviate the on-target/off-tumor toxicity. The affinities of scFvs for different antigens were also summarized to designate a relatively optimal working range for CAR design. Last, a synthetic biology approach utilizing a low-affinity synthetic Notch (synNotch) receptor to achieve ultrasensitivity of antigen-density discrimination and murine models to assay the on-target/off-tumor toxicity of CARs were highlighted. Thus, this review provides preliminary guidelines of choosing the right scFvs for CARs.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-021-04089-x