Chimeric antigen receptor T cells therapy in solid tumors.
CAR-T therapy
Cytokine release syndrome
Human leukocyte antigen
Tumor
Tumor microenvironment
Tumor toxicity
Journal
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
ISSN: 1699-3055
Titre abrégé: Clin Transl Oncol
Pays: Italy
ID NLM: 101247119
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
13
01
2023
accepted:
10
02
2023
medline:
28
6
2023
pubmed:
1
3
2023
entrez:
28
2
2023
Statut:
ppublish
Résumé
Chimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. Chimeric antigen receptor (CAR) is an engineered synthetic receptor of CAR-T, which give T cells the ability to recognize tumor antigens in a human leukocyte antigen-independent (HLA-independent) manner and enables them to recognize more extensive target antigens than natural T cell surface receptor (TCR), resulting in tumor destruction. CAR-T is composed of an extracellular single-chain variable fragment (scFv) of antibody, which serves as the targeting moiety, hinge region, transmembrane spacer, and intracellular signaling domain(s). CAR-T has been developing in many generations, which differ according to costimulatory domains. CAR-T therapy has several limitations that reduce its wide availability in immunotherapy which we can summarize in antigen escape that shows either partial or complete loss of target antigen expression, so multiplexing CAR-T cells are promoted to enhance targeting of tumor profiles. In addition, the large diversity in the tumor microenvironment also plays a major role in limiting this kind of treatment. Therefore, engineered CAR-T cells can evoke immunostimulatory signals that rebalance the tumor microenvironment. Using CAR-T therapy in treating the solid tumor is mainly restricted by the difficulty of CAR-T cells infiltrating the tumor site, so local administration was developed to improve the quality of treatment. The most severe toxicity after CAR-T therapy is on-target/on-tumor toxicity, such as cytokine release syndrome (CRS). Another type of toxicity is on-target/off-tumor toxicity which originates from the binding of CAR-T cells to target antigen that has shared expression on normal cells leading to damage in healthy cells and organs. Toxicity management should become a focus of implementation to permit management beyond specialized centers.
Identifiants
pubmed: 36853399
doi: 10.1007/s12094-023-03122-8
pii: 10.1007/s12094-023-03122-8
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2279-2296Informations de copyright
© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).
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