Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers
Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refracto...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444701 |
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| author | Miriam Velasco-Sidro Javier Arroyo-Ródenas Laura Díez-Alonso Ángel Ramírez-Fernández Luis Álvarez-Vallina |
| author_facet | Miriam Velasco-Sidro Javier Arroyo-Ródenas Laura Díez-Alonso Ángel Ramírez-Fernández Luis Álvarez-Vallina |
| author_sort | Miriam Velasco-Sidro |
| collection | DOAJ |
| description | Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments. In fact, several clinical trials targeting both antigens through different strategies are currently underway. Here, based on the previously validated STAb (in situ secretion of T cell-redirecting bispecific antibodies) concept, we used two different engineering strategies (pool and co-transduction) to generate dual-targeted STAb-T cells simultaneously secreting BCMA TCE and CD19 TCE that outperformed single-targeted STAb-T cells in different in vitro models. These promising results encourage further preclinical clinical testing of dual STAb-T cells in R/R B-cell malignancies. |
| format | Article |
| id | doaj-art-e3a2bc73794648e387bd6fd236704344 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-e3a2bc73794648e387bd6fd2367043442024-12-26T13:16:23ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2444701Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancersMiriam Velasco-Sidro0Javier Arroyo-Ródenas1Laura Díez-Alonso2Ángel Ramírez-Fernández3Luis Álvarez-Vallina4Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, SpainCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, SpainCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, SpainCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, SpainCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, SpainDespite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments. In fact, several clinical trials targeting both antigens through different strategies are currently underway. Here, based on the previously validated STAb (in situ secretion of T cell-redirecting bispecific antibodies) concept, we used two different engineering strategies (pool and co-transduction) to generate dual-targeted STAb-T cells simultaneously secreting BCMA TCE and CD19 TCE that outperformed single-targeted STAb-T cells in different in vitro models. These promising results encourage further preclinical clinical testing of dual STAb-T cells in R/R B-cell malignancies.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444701Bispecific antibodiesdual-targeting immunotherapyhaematological malignanciesSTAb-T immunotherapyT cell engagers |
| spellingShingle | Miriam Velasco-Sidro Javier Arroyo-Ródenas Laura Díez-Alonso Ángel Ramírez-Fernández Luis Álvarez-Vallina Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers OncoImmunology Bispecific antibodies dual-targeting immunotherapy haematological malignancies STAb-T immunotherapy T cell engagers |
| title | Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers |
| title_full | Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers |
| title_fullStr | Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers |
| title_full_unstemmed | Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers |
| title_short | Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers |
| title_sort | dual targeted stab t cells secreting bcma and cd19 t cell engagers for improved control of haematological cancers |
| topic | Bispecific antibodies dual-targeting immunotherapy haematological malignancies STAb-T immunotherapy T cell engagers |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444701 |
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