Cytotoxicity of the CD3xCD20 bispecific antibody epcoritamab in CLL is increased by concurrent BTK or Bcl-2 targeting
| العنوان: | Cytotoxicity of the CD3xCD20 bispecific antibody epcoritamab in CLL is increased by concurrent BTK or Bcl-2 targeting |
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| المؤلفون: | Maissa Mhibik, Erika M Gaglione, David Eik, John Herrick, Janet Le, Inhye E Ahn, Christopher Chiu, Monica Wielgos-Bonvallet, Ida H Hiemstra, Esther CW Breij, Jenny Chen, Edward B Reilly, Pearlie K. Epling-Burnette, Edith Szafer Glusman, Clare Sun, Adrian Wiestner |
| المصدر: | Blood Advances. |
| بيانات النشر: | American Society of Hematology, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Hematology |
| الوصف: | Chronic lymphocytic leukemia (CLL) is an immunosuppressive disease characterized by increased infectious morbidity and inferior anti-tumor activity of immunotherapies. Targeted therapy with Bruton's tyrosine kinase inhibitors (BTKis), or the Bcl-2 inhibitor venetoclax, have profoundly improved treatment outcomes in CLL. To overcome or prevent drug resistance and extend duration of response after time-limited therapy, combination regimens are tested. Anti-CD20 antibodies that recruit cell and complement mediated effector functions are commonly used. Epcoritamab (GEN3013), an anti-CD3xCD20 bispecific antibody (bsAb) that recruits T cell effector functions, has demonstrated potent clinical activity in patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma. Development in CLL is ongoing. To characterize epcoritamab mediated cytotoxicity against primary CLL cells, peripheral blood mononuclear cells (PBMCs) from treatment-naïve and BTKi-treated patients, including patients progressing on therapy were cultured with epcoritamab alone or in combination with venetoclax. Ongoing treatment with a BTKi and high effector:target ratios were associated with superior in vitro cytotoxicity. Cytotoxic activity was independent of CD20 expression on CLL cells, and observed in samples from patients progressing on a BTKi. Epcoritamab induced significant T-cell expansion, activation, and differentiation into Th1 and effector memory cells, in all patient samples. In patient-derived xenografts, epcoritamab reduced blood and spleen disease burden compared to mice receiving a non-targeting control. In vitro, the combination of venetoclax with epcoritamab induced superior killing of CLL cells than either agent alone. These data support the investigation of epcoritamab in combination with BTKis or venetoclax to consolidate responses and target emergent drug resistant subclones. |
| تدمد: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2022009517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::dcae76acd97efcd6a93cfb0fc7587566 https://doi.org/10.1182/bloodadvances.2022009517 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........dcae76acd97efcd6a93cfb0fc7587566 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24739537 24739529 |
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| DOI: | 10.1182/bloodadvances.2022009517 |