AUTHOR=Smirnov Sergei , Mateikovich Polina , Samochernykh Konstantin , Shlyakhto Evgeny 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1335424

DOI=10.3389/fimmu.2024.1335424

ISSN=1664-3224

ABSTRACT=<p>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.</p>