A single-chain antibody generation system yielding CAR-T cells with superior antitumor function.
Animals
Female
Humans
Immunoglobulin Heavy Chains
/ genetics
Immunoglobulin Light Chains
/ genetics
Immunoglobulin Variable Region
/ genetics
Immunological Synapses
Immunotherapy, Adoptive
Jurkat Cells
K562 Cells
Lymphoma
/ genetics
Mice, Inbred NOD
Mice, SCID
Receptors, Chimeric Antigen
/ genetics
Single-Chain Antibodies
/ genetics
T-Lymphocytes
/ immunology
Tumor Burden
Xenograft Model Antitumor Assays
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
02 03 2021
02 03 2021
Historique:
received:
18
09
2020
accepted:
03
02
2021
entrez:
3
3
2021
pubmed:
4
3
2021
medline:
11
8
2021
Statut:
epublish
Résumé
Cancer immunotherapy using T cells redirected with chimeric antigen receptor (CAR) has shown a lot of promise. We have established a single-chain antibody (scFv) generation system in which scFv library-expressing CAR-T cells can be screened appropriately based on their antitumor functions. A variable region library containing the variable and J regions of the human immunoglobulin light or heavy chain was fused with the variable region of a heavy or light chain encoded by an existing tumor-specific antibody to generate a new scFv library. Then, scFv library-expressing CAR-T cells were generated and stimulated with target cells to concentrate the antigen-specific population. Using this system, target-specific recognition of CAR-T cells appeared to be finely tuned by selecting a new variable region. Importantly, we have demonstrated that the newly optimized scFv-expressing CAR-T cells had better proliferation capacity and durable phenotypes, enabling superior reactivity against advanced tumors in vivo in comparison with the original CAR-T cells. Therefore, the optimization of an scFv is needed to maximize the in vivo antitumor functions of CAR-T cells. This system may allow us to adjust an immunological synapse formed by an scFv expressed by CAR-T cells and a target antigen, representing an ideal form of CAR-T-cell immunotherapy.
Identifiants
pubmed: 33654176
doi: 10.1038/s42003-021-01791-1
pii: 10.1038/s42003-021-01791-1
pmc: PMC7925539
doi:
Substances chimiques
Immunoglobulin Heavy Chains
0
Immunoglobulin Light Chains
0
Immunoglobulin Variable Region
0
Receptors, Chimeric Antigen
0
Single-Chain Antibodies
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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