biostudies-literatureUnknown14(1)Gomez-Rosel MAdoptive 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 (<b>S</b>ecretion of <b>T</b> 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 effOncoimmunology2570224https://www.ebi.ac.uk/biostudies/studies/S-EPMC12562732biostudies-literatureSimultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager.PMC12562732Gomez-Rosel MRubio-Perez LDiez-Alonso LAlvarez-Vallina LZagorac IHangiu ONavarro RCompte MBlanco BTorres-Ruiz RRodriguez-Perales SBlanco FJDominguez-Alonso CfalseSimultaneous 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 (<b>S</b>ecretion of <b>T</b> 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 eff2025-01-01T00:00:00Z2025 Dec2026-06-05T09:22:32.558Z2026-05-15T03:12:20.208ZS-EPMC125627324113995310.1080/2162402X.2025.2570224