دورية أكاديمية
Murlentamab, a Low Fucosylated Anti-Müllerian Hormone Type II Receptor (AMHRII) Antibody, Exhibits Anti-Tumor Activity through Tumor-Associated Macrophage Reprogrammation and T Cell Activation
| العنوان: | Murlentamab, a Low Fucosylated Anti-Müllerian Hormone Type II Receptor (AMHRII) Antibody, Exhibits Anti-Tumor Activity through Tumor-Associated Macrophage Reprogrammation and T Cell Activation |
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| المؤلفون: | Mélissa Prat, Marie Salon, Thibault Allain, Olivier Dubreuil, Grégory Noël, Laurence Preisser, Bérangère Jean, Lydie Cassard, Fanny Lemée, Isabelle Tabah-Fish, Bernard Pipy, Pascale Jeannin, Jean-François Prost, Jean-Marc Barret, Agnès Coste |
| المصدر: | Cancers, Vol 13, Iss 8, p 1845 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | murlentamab, glyco-engineered antibody, tumor-associated macrophages, ovarian cancer, adaptive immunity, immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | AMHRII, the anti-Müllerian hormone receptor, is selectively expressed in normal sexual organs but is also re-expressed in gynecologic cancers. Hence, we developed murlentamab, a humanized glyco-engineered anti-AMHRII monoclonal antibody currently in clinical trial. Low-fucosylated antibodies are known to increase the antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) potency of effector cells, but some preliminary results suggest a more global murlentamab-dependent activation of the immune system. In this context, we demonstrate here that the murlentamab opsonization of AMHRII-expressing ovarian tumor cells, in the presence of unstimulated- or tumor-associated macrophage (TAM)-like macrophages, significantly promotes macrophage-mediated ADCC and shifts the whole microenvironment towards a pro-inflammatory and anti-tumoral status, thus triggering anti-tumor activity. We also report that murlentamab orients both unstimulated- and TAM-like macrophages to an M1-like phenotype characterized by a strong expression of co-stimulation markers, pro-inflammatory cytokines and chemokines, favoring T cell recruitment and activation. Moreover, we show that murlentamab treatment shifts CD4+ Th1/Th2 balance towards a Th1 response and activates CD8+ T cells. Altogether, these results suggest that murlentamab, through naïve macrophage orientation and TAM reprogrammation, stimulates the anti-tumor adaptive immune response. Those mechanisms might contribute to the sustained clinical benefit observed in advanced cancer patients treated with murlentamab. Finally, the enhanced murlentamab activity in combination with pembrolizumab opens new therapeutic perspectives. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 13081845 2072-6694 |
| Relation: | https://www.mdpi.com/2072-6694/13/8/1845; https://doaj.org/toc/2072-6694 |
| DOI: | 10.3390/cancers13081845 |
| URL الوصول: | https://doaj.org/article/5522b2340f504a75be168a55f75881b5 |
| رقم الأكسشن: | edsdoj.5522b2340f504a75be168a55f75881b5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 13081845 20726694 |
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| DOI: | 10.3390/cancers13081845 |