Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy.


Journal

Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937

Informations de publication

Date de publication:
25 10 2023
Historique:
received: 24 08 2023
accepted: 12 10 2023
medline: 27 10 2023
pubmed: 26 10 2023
entrez: 26 10 2023
Statut: epublish

Résumé

T cell differentiation is a highly regulated, multi-step process necessary for the progressive establishment of effector functions, immunological memory, and long-term control of pathogens. In response to strong stimulation, as seen in severe or chronic infections or cancer, T cells acquire a state of hypo-responsiveness known as exhaustion, limiting their effector function. Recent advances in autologous chimeric antigen receptor (CAR)-T cell therapies have revolutionized the treatment of hematologic malignancies by taking advantage of the basic principles of T cell biology to engineer products that promote long-lasting T cell response. However, many patients' malignancies remain unresponsive to treatment or are prone to recur. Discoveries in T cell biology, including the identification of key regulators of differentiation and exhaustion, offer novel opportunities to have a durable impact on the fate of CAR-T cells after infusion. Such next-generation CAR-T cell therapies and their clinical implementation may result in the next leap forward in cancer treatment for selected patients. In this context, this review summarizes the foundational principles of T cell differentiation and exhaustion and describes how they can be utilized and targeted to further improve the design and efficacy of CAR-T cell therapies.

Identifiants

pubmed: 37880715
doi: 10.1186/s13045-023-01504-7
pii: 10.1186/s13045-023-01504-7
pmc: PMC10601191
doi:

Substances chimiques

Receptors, Chimeric Antigen 0

Types de publication

Journal Article Review Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Yannick Bulliard (Y)

Appia Bio, 6160 Bristol Pkwy, Culver City, CA, 90230, USA.

Borje S Andersson (BS)

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

Mehmet A Baysal (MA)

Unit 455, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.

Jason Damiano (J)

Appia Bio, 6160 Bristol Pkwy, Culver City, CA, 90230, USA.

Apostolia M Tsimberidou (AM)

Unit 455, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. atsimber@mdanderson.org.

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