Exploring Synergistic Approaches to Enhance Blinatumomab's Efficacy in Acute Lymphoblastic Leukemia
Resistance to blinatumomab (CD19-CD3 BiTE) is a significant obstacle in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), prompting the investigation of novel drug combinations. We aimed to generate an "in vitro" model capable of identifying synergistic combinations...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/221187 |
| Acceso en línea: | https://hdl.handle.net/2445/221187 |
| Access Level: | acceso abierto |
| Palabra clave: | Leucèmia Leucèmia limfocítica crònica Medicaments Leukemia Chronic lymphocytic leukemia Drugs |
| Sumario: | Resistance to blinatumomab (CD19-CD3 BiTE) is a significant obstacle in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), prompting the investigation of novel drug combinations. We aimed to generate an "in vitro" model capable of identifying synergistic combinations to enhance blinatumomab's efficacy in BCP-ALL treatment. Drug response profiling used annexin V/propidium iodide/CD3 staining and flow cytometry analysis in 28 patient samples and 4 cell lines. Co-cultured with healthy donor T-cells, samples were treated for 24h with blinatumomab and/or other inhibitors. Differential sensitivity to blinatumomab was observed among patient samples and cell lines. Idelalisib (tyrosin kinase inhibitor; TKi) combined with blinatumomab exhibited potential antagonistic effects. Birinapant (SMAC mimetic) and venetoclax (BCL2 inhibitor) demonstrated increased efficacy in BCP-ALL cell lines, displaying synergistic potential with blinatumomab. Our findings support TKi and SMAC mimetics' immunomodulatory effects, in accordance to prior anti-CD19 CAR T cell reports. Venetoclax emerges as a promising candidate for combination therapy against blinatumomab resistance. |
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