Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager

22 páginas, 5 figuras

Bibliographic Details
Authors: Gómez-Rosel, Marina, Rubio-Pérez, Laura, Zagorac, Ivana, Domínguez-Alonso, Carmen, Díez-Alonso, Laura, Hangiu, Oana, Navarro, Rocío, Torres-Ruiz, Raúl, Rodriguez-Perales, Sandra, Blanco, Francisco J., Compte, Marta, Álvarez-Vallina, Luis, Blanco, Belén
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/406059
Online Access:http://hdl.handle.net/10261/406059
Access Level:Open access
Keyword:4-1BB costimulation
PD−1/PD-L1 blockers
STAb-T cells
bispecific antibodies
id ES_3831a3db4ecb83a3f8f8570a9a5eecd0
oai_identifier_str oai:digital.csic.es:10261/406059
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
title Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
spellingShingle Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
Gómez-Rosel, Marina
4-1BB costimulation
PD−1/PD-L1 blockers
STAb-T cells
bispecific antibodies
title_short Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
title_full Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
title_fullStr Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
title_full_unstemmed Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
title_sort Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager
dc.creator.none.fl_str_mv Gómez-Rosel, Marina
Rubio-Pérez, Laura
Zagorac, Ivana
Domínguez-Alonso, Carmen
Díez-Alonso, Laura
Hangiu, Oana
Navarro, Rocío
Torres-Ruiz, Raúl
Rodriguez-Perales, Sandra
Blanco, Francisco J.
Compte, Marta
Álvarez-Vallina, Luis
Blanco, Belén
author Gómez-Rosel, Marina
author_facet Gómez-Rosel, Marina
Rubio-Pérez, Laura
Zagorac, Ivana
Domínguez-Alonso, Carmen
Díez-Alonso, Laura
Hangiu, Oana
Navarro, Rocío
Torres-Ruiz, Raúl
Rodriguez-Perales, Sandra
Blanco, Francisco J.
Compte, Marta
Álvarez-Vallina, Luis
Blanco, Belén
author_role author
author2 Rubio-Pérez, Laura
Zagorac, Ivana
Domínguez-Alonso, Carmen
Díez-Alonso, Laura
Hangiu, Oana
Navarro, Rocío
Torres-Ruiz, Raúl
Rodriguez-Perales, Sandra
Blanco, Francisco J.
Compte, Marta
Álvarez-Vallina, Luis
Blanco, Belén
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Científica Asociación Española Contra el Cáncer
Comunidad de Madrid
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Fundación CRIS contra el Cáncer
La Caixa
Fundación Fero
Blanco, Francisco J. [0000-0003-2545-4319]
Gómez-Rosel, Marina [0000-0001-8816-9844]
Rubio-Pérez, Laura [0000-0002-2877-6092]
Zagorac, Ivana [0000-0002-7135-8283]
Domínguez-Alonso, Carmen [0000-0002-0446-9629]
Díez-Alonso, Laura [0000-0002-9545-6910]
Hangiu, Oana [0000-0002-2641-8531]
Navarro, Rocío [0000-0002-0083-7711]
Compte, Marta [0000-0002-7138-9266]
Álvarez-Vallina, Luis [0000-0003-3053-6757]
Blanco, Belén [0000-0001-5085-7756]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv 4-1BB costimulation
PD−1/PD-L1 blockers
STAb-T cells
bispecific antibodies
topic 4-1BB costimulation
PD−1/PD-L1 blockers
STAb-T cells
bispecific antibodies
description 22 páginas, 5 figuras
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
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/10261/406059
url http://hdl.handle.net/10261/406059
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01030
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI23%2F01256
IND2022/BMD−23732/
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148429OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117323RB-I00
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/DTS20%2F00089
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-152271NB-I00
P2022/BMD−7225/
https://doi.org/10.1080/2162402X.2025.2570224
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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_ 1869406085163515904
spelling Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engagerGómez-Rosel, MarinaRubio-Pérez, LauraZagorac, IvanaDomínguez-Alonso, CarmenDíez-Alonso, LauraHangiu, OanaNavarro, RocíoTorres-Ruiz, RaúlRodriguez-Perales, SandraBlanco, Francisco J.Compte, MartaÁlvarez-Vallina, LuisBlanco, Belén4-1BB costimulationPD−1/PD-L1 blockersSTAb-T cellsbispecific antibodies22 páginas, 5 figurasAdoptive therapy with CAR-T cells and systemic administration of bispecific T-cell engagers (TCE) have achieved unprecedented success in the treatment of relapsed/refractory (R/R) B-cell malignancies. However, high relapse rates remain a major challenge. STAb (Secretion of T cell-redirecting bispecific Antibodies)-T-cell immunotherapy represents a promising alternative by enabling both polyclonal T-cell recruitment and sustained bispecific antibody release. Here, we describe an evolution of STAb-T19 therapy, which has demonstrated superior outcomes to those of CAR-T-19 cells in preclinical models of B-ALL, on the basis of the simultaneous secretion of two bispecific antibodies: a CD19 × CD3 TCE and a PD-L1 × 4-1BB bsAb. The combined approach aims to increase the antitumor efficacy of STAb-T19 cells by blocking the PD-1/PD-L1 axis with conditional 4-1BB costimulation to ensure the long-term persistence of STAb-T cells. Preclinical data show that this combination improves cytotoxic activity and prolongs antileukemic efficacy compared with low-dose single STAb-T therapy. Our findings suggest that the integration of PD-L1 × 4-1BB bsAbs into STAb-T19 therapy may maximize efficacy, thereby opening a promising avenue to address resistance and relapse in B-ALL. Moreover, this approach may pave the way for the development of next-generation cell-based therapies for hematologic and solid malignancies.BB is funded by Fundación Científica de la Asociación Española Contra el Cáncer (INNOV211832BLAN), the Comunidad de Madrid (IND2022/BMD−23732) and the Instituto de Salud Carlos III (ISCIII) (PI20/01030, PI23/01256). LA-V is funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 (PID2023-148429OB-I00, PID2020-117323RB-I00, PDC2021−121711-I00, CPP2022−009762, CPP2022−009765, CPP2023−010827), ISCIII (DTS20/ 00089, PMPTA22/00167), the Asociación Española contra el Cáncer (PROYE19084ALVA and PRYGN234844ALVA), the CRIS Cancer Foundation (FCRIS−2021−0090 and FCRIS−2023−0070), the Fundación ‘‘La Caixa’’ (HR21−00761 project IL7R_LungCan), the Comunidad de Madrid (P2022/BMD−7225 Next Generation CART MAD), and the Fundación FERO (BBASELGAFERO2024.01). M.G.-R. is supported by an industrial PhD fellowship from the Comunidad de Madrid (IND2022/BMD−23732). FJB is funded by PID2023-152271NB-I00 from MCIN/AEI/10.13039/501100011033. We thank the Proteomics service at CIC bioGUNE and the Molecular Interactions service at CIB-CSIC for assisting with the mass spectrometry and SEC-MALS experiments. This study has adhered to ARRIVE guidelinesPeer reviewedTaylor & FrancisFundación Científica Asociación Española Contra el CáncerComunidad de MadridInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)Fundación CRIS contra el CáncerLa CaixaFundación FeroBlanco, Francisco J. [0000-0003-2545-4319]Gómez-Rosel, Marina [0000-0001-8816-9844]Rubio-Pérez, Laura [0000-0002-2877-6092]Zagorac, Ivana [0000-0002-7135-8283]Domínguez-Alonso, Carmen [0000-0002-0446-9629]Díez-Alonso, Laura [0000-0002-9545-6910]Hangiu, Oana [0000-0002-2641-8531]Navarro, Rocío [0000-0002-0083-7711]Compte, Marta [0000-0002-7138-9266]Álvarez-Vallina, Luis [0000-0003-3053-6757]Blanco, Belén [0000-0001-5085-7756]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/406059reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01030info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI23%2F01256IND2022/BMD−23732/info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148429OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117323RB-I00info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/DTS20%2F00089info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-152271NB-I00P2022/BMD−7225/https://doi.org/10.1080/2162402X.2025.2570224Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4060592026-05-22T06:33:51Z
score 15.811543

Similar Items