Tuning the ignition of CAR: optimizing the affinity of scFv to improve CAR-T therapy.
Cell Mol Life Sci
; 79(1): 14, 2021 Dec 29.
Article
em En
| MEDLINE
| ID: mdl-34966954
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
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Anticorpos de Cadeia Única
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Receptores de Antígenos Quiméricos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article