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

Adoptive 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 bispeci...

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Autores: Gómez-Rosel, M, Rubio-Pérez, L, Zagorac, I, Domínguez-Alonso, C, Díez-Alonso, L, Hangiu, O, Navarro, R, Torres-Ruíz, R, Rodríguez-Perales, S, Blanco, FJ, Compte, M, Alvarez-Vallina, L, Blanco, B
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p4531
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4531
Access Level:acceso abierto
Palabra clave:STAb-T cells
bispecific antibodies
PD-1/PD-L1 blockers
4-1BB costimulation
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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, MRubio-Pérez, LZagorac, IDomínguez-Alonso, CDíez-Alonso, LHangiu, ONavarro, RTorres-Ruíz, RRodríguez-Perales, SBlanco, FJCompte, MAlvarez-Vallina, LBlanco, BSTAb-T cellsbispecific antibodiesPD-1/PD-L1 blockers4-1BB costimulationAdoptive 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 x CD3 TCE and a PD-L1 x 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 x 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.TAYLOR & FRANCIS INC2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4531OncoImmunologyISSN: 2162402XISSNl: 21624011reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p45312026-06-17T11:19:47Z
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, M
STAb-T cells
bispecific antibodies
PD-1/PD-L1 blockers
4-1BB costimulation
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, M
Rubio-Pérez, L
Zagorac, I
Domínguez-Alonso, C
Díez-Alonso, L
Hangiu, O
Navarro, R
Torres-Ruíz, R
Rodríguez-Perales, S
Blanco, FJ
Compte, M
Alvarez-Vallina, L
Blanco, B
author Gómez-Rosel, M
author_facet Gómez-Rosel, M
Rubio-Pérez, L
Zagorac, I
Domínguez-Alonso, C
Díez-Alonso, L
Hangiu, O
Navarro, R
Torres-Ruíz, R
Rodríguez-Perales, S
Blanco, FJ
Compte, M
Alvarez-Vallina, L
Blanco, B
author_role author
author2 Rubio-Pérez, L
Zagorac, I
Domínguez-Alonso, C
Díez-Alonso, L
Hangiu, O
Navarro, R
Torres-Ruíz, R
Rodríguez-Perales, S
Blanco, FJ
Compte, M
Alvarez-Vallina, L
Blanco, B
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv STAb-T cells
bispecific antibodies
PD-1/PD-L1 blockers
4-1BB costimulation
topic STAb-T cells
bispecific antibodies
PD-1/PD-L1 blockers
4-1BB costimulation
description Adoptive 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 x CD3 TCE and a PD-L1 x 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 x 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4531
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4531
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv TAYLOR & FRANCIS INC
publisher.none.fl_str_mv TAYLOR & FRANCIS INC
dc.source.none.fl_str_mv OncoImmunology
ISSN: 2162402X
ISSNl: 21624011
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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