Recent advances on CAR-T signaling pave the way for prolonged persistence and new modalities in clinic

Sergei Smirnov; Polina Mateikovich; Konstantin Samochernykh; Evgeny Shlyakhto

doi:10.3389/fimmu.2024.1335424

Recent advances on CAR-T signaling pave the way for prolonged persistence and new modalities in clinic

Front Immunol. 2024 Feb 22:15:1335424. doi: 10.3389/fimmu.2024.1335424. eCollection 2024.

Authors

Sergei Smirnov¹, Polina Mateikovich¹, Konstantin Samochernykh¹, Evgeny Shlyakhto¹

Affiliation

¹ Almazov National Medical Research Centre, Personalized Medicine Centre, Saint Petersburg, Russia.

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies. The importance of the receptor costimulatory domain for long-term CAR-T cell engraftment and therapeutic efficacy was demonstrated with second-generation CAR-T cells. Fifth generation CAR-T cells are currently in preclinical trials. At the same time, the processes that orchestrate the activation and differentiation of CAR-T cells into a specific phenotype that predisposes them to long-term persistence are not fully understood. This review highlights ongoing research aimed at elucidating the role of CAR domains and T-cell signaling molecules involved in these processes.

Keywords: CAR (chimeric antigen receptor); T cell; activation; costimulatory; immunotherapy; persistence; signaling.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Hematologic Neoplasms* / drug therapy
Humans
Immunotherapy, Adoptive
Receptors, Chimeric Antigen*
Signal Transduction
T-Lymphocytes

Substances

Receptors, Chimeric Antigen

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation, agreement No. 075-15-2022-301 dated by 20.04.2024.