Challenges in the preclinical design and assessment of CAR-T cells

Tomai, Radu; De Las Rivas, Javier; Fetica, Bogdan; Bergantim, Rui; Filipic, Brankica; Gagic, Zarko; Nikolic, Katarina; Gulei, Diana; Kegyes, David; Nistor, Madalina; Muresan, Ximena María; Cenariu, Diana; Feder, Richard; Pavel-Tanasa, Mariana; Cianga, Andrei; Bogdan Tigu, Adrián; Munteanu, Raluca; Tanase, Alina; Einsele, Hermann; Tomuleasa, Ciprian

Challenges in the preclinical design and assessment of CAR-T cells

The advent of immunotherapy in the treatment of cancer has opened a new dimension in the management of this complex multifaceted disease, bringing hope to many patients whose tumors have failed to respond to conventional therapies. The adoptive T cell therapy has since been extended to the treatment...

ver descrição completa

Detalhes bibliográficos
Autores:	Tomai, Radu, De Las Rivas, Javier, Fetica, Bogdan, Bergantim, Rui, Filipic, Brankica, Gagic, Zarko, Nikolic, Katarina, Gulei, Diana, Kegyes, David, Nistor, Madalina, Muresan, Ximena María, Cenariu, Diana, Feder, Richard, Pavel-Tanasa, Mariana, Cianga, Andrei, Bogdan Tigu, Adrián, Munteanu, Raluca, Tanase, Alina, Einsele, Hermann, Tomuleasa, Ciprian
Formato:	artículo
Estado:	Versión publicada
Fecha de publicación:	2025
País:	España
Recursos:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/423459
Acesso em linha:	http://hdl.handle.net/10261/423459
Access Level:	acceso abierto
Palavra-chave:	CAR-T cell tracking Tumor organoids Antigen escape Solid tumor immunotherapy Metabolic reprogramming HDAC inhibitors

id	ES_2ace6e73ac91bf2e87d4f66d83b08d2c
oai_identifier_str	oai:digital.csic.es:10261/423459
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	Challenges in the preclinical design and assessment of CAR-T cellsTomai, RaduDe Las Rivas, JavierFetica, BogdanBergantim, RuiFilipic, BrankicaGagic, ZarkoNikolic, KatarinaGulei, DianaKegyes, DavidNistor, MadalinaMuresan, Ximena MaríaCenariu, DianaFeder, RichardPavel-Tanasa, MarianaCianga, AndreiBogdan Tigu, AdriánMunteanu, RalucaTanase, AlinaEinsele, HermannTomuleasa, CiprianCAR-T cell trackingTumor organoidsAntigen escapeSolid tumor immunotherapyMetabolic reprogrammingHDAC inhibitorsThe advent of immunotherapy in the treatment of cancer has opened a new dimension in the management of this complex multifaceted disease, bringing hope to many patients whose tumors have failed to respond to conventional therapies. The adoptive T cell therapy has since been extended to the treatment of several hematologic malignancies, initially in relapsed settings and more recently at the forefront of treatment due to high response rates. Despite exciting initial results, the preclinical antitumor effects of the first long-term studies show that CAR (Chimeric Antigen Receptor)-T cells have been slow to translate to the clinical setting, with early clinical trials showing suboptimal responses. The main reasons for the limited clinical performance seemed to be related to the low activation and short persistence of CAR-T cells. Thus, began a journey to improve the initial CAR structure, leading to the development of more complex constructs, which are grouped into five CAR generations. In this review, we describe the main challenges and potential solutions for the evaluation of CAR T-cell-based therapies in the preclinical setting.This article is based upon work from COST Action IMMUNO-model, CA21135, supported by COST (European Cooperation in Science and Technology (KF, RB, BoF, DC, RM and CT). DK is funded by a national research grant of the Romanian Government – Bursa Henri Coanda, contract 8/10.02.2024. CT is funded by an international grant of the European Hematology Association (EHA-SWG Immunotherapy Project 2024—CAR NK cells for tumor associated macrophage immunomodulation—a new era of immunotherapy), as well as by a bilateral collaboration grant between Romania and Moldova (PN-IV-P8-8.3-ROMD-2023-0036). HE is funded by a national grant of the Romanian Research Ministry—PNRR 2024-2026 (PNRR/2022/C9/MCID/18, Contract No. 760278/26.03.2024). MPT and AC are funded by a national grant of the Romanian Research Ministry—CNCS-UEFISCDI project number PN-IV-P2-2.1-TE-2023-1182 within PNCDI IV.Peer reviewedFrontiers MediaEuropean Cooperation in Science and TechnologyEuropean Hematology AssociationMinistry of Research and Innovation (Romania)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/423459reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3389/fimmu.2025.1564998Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4234592026-05-22T06:33:51Z
dc.title.none.fl_str_mv	Challenges in the preclinical design and assessment of CAR-T cells
title	Challenges in the preclinical design and assessment of CAR-T cells
spellingShingle	Challenges in the preclinical design and assessment of CAR-T cells Tomai, Radu CAR-T cell tracking Tumor organoids Antigen escape Solid tumor immunotherapy Metabolic reprogramming HDAC inhibitors
title_short	Challenges in the preclinical design and assessment of CAR-T cells
title_full	Challenges in the preclinical design and assessment of CAR-T cells
title_fullStr	Challenges in the preclinical design and assessment of CAR-T cells
title_full_unstemmed	Challenges in the preclinical design and assessment of CAR-T cells
title_sort	Challenges in the preclinical design and assessment of CAR-T cells
dc.creator.none.fl_str_mv	Tomai, Radu De Las Rivas, Javier Fetica, Bogdan Bergantim, Rui Filipic, Brankica Gagic, Zarko Nikolic, Katarina Gulei, Diana Kegyes, David Nistor, Madalina Muresan, Ximena María Cenariu, Diana Feder, Richard Pavel-Tanasa, Mariana Cianga, Andrei Bogdan Tigu, Adrián Munteanu, Raluca Tanase, Alina Einsele, Hermann Tomuleasa, Ciprian
author	Tomai, Radu
author_facet	Tomai, Radu De Las Rivas, Javier Fetica, Bogdan Bergantim, Rui Filipic, Brankica Gagic, Zarko Nikolic, Katarina Gulei, Diana Kegyes, David Nistor, Madalina Muresan, Ximena María Cenariu, Diana Feder, Richard Pavel-Tanasa, Mariana Cianga, Andrei Bogdan Tigu, Adrián Munteanu, Raluca Tanase, Alina Einsele, Hermann Tomuleasa, Ciprian
author_role	author
author2	De Las Rivas, Javier Fetica, Bogdan Bergantim, Rui Filipic, Brankica Gagic, Zarko Nikolic, Katarina Gulei, Diana Kegyes, David Nistor, Madalina Muresan, Ximena María Cenariu, Diana Feder, Richard Pavel-Tanasa, Mariana Cianga, Andrei Bogdan Tigu, Adrián Munteanu, Raluca Tanase, Alina Einsele, Hermann Tomuleasa, Ciprian
author2_role	author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	European Cooperation in Science and Technology European Hematology Association Ministry of Research and Innovation (Romania) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	CAR-T cell tracking Tumor organoids Antigen escape Solid tumor immunotherapy Metabolic reprogramming HDAC inhibitors
topic	CAR-T cell tracking Tumor organoids Antigen escape Solid tumor immunotherapy Metabolic reprogramming HDAC inhibitors
description	The advent of immunotherapy in the treatment of cancer has opened a new dimension in the management of this complex multifaceted disease, bringing hope to many patients whose tumors have failed to respond to conventional therapies. The adoptive T cell therapy has since been extended to the treatment of several hematologic malignancies, initially in relapsed settings and more recently at the forefront of treatment due to high response rates. Despite exciting initial results, the preclinical antitumor effects of the first long-term studies show that CAR (Chimeric Antigen Receptor)-T cells have been slow to translate to the clinical setting, with early clinical trials showing suboptimal responses. The main reasons for the limited clinical performance seemed to be related to the low activation and short persistence of CAR-T cells. Thus, began a journey to improve the initial CAR structure, leading to the development of more complex constructs, which are grouped into five CAR generations. In this review, we describe the main challenges and potential solutions for the evaluation of CAR T-cell-based therapies in the preclinical setting.
publishDate	2025
dc.date.none.fl_str_mv	2025 2026 2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/423459
url	http://hdl.handle.net/10261/423459
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	https://doi.org/10.3389/fimmu.2025.1564998 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Frontiers Media
publisher.none.fl_str_mv	Frontiers Media
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
collection	DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869405095657996288
score	15,811543

Challenges in the preclinical design and assessment of CAR-T cells

Registos relacionados