Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma
In: Molecular Therapy Oncolytics, Jg. 21 (2021-04-01), S. 158-170
Online
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Zugriff:
Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib and anti-CD20 antibodies like rituximab were designed as a backbone in many clinical trials. However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab’s antibody-dependent cellular cytotoxicity (ADCC) efficacy. Orelabrutinib (Orel), a novel BTK inhibitor, was designed with high selectivity to BTK. In our study, we demonstrated in preclinical models that orelabrutinib in combination with rituximab could preserve NK-cell-mediated ADCC induced by rituximab and enhanced the apoptosis of tumor cells in vitro. The addition of orelabrutinib to rituximab had produced promising combined anti-tumor effects in B cell lymphomas in vivo. Collectively, combination therapy of orelabrutinib with rituximab would benefit patients with B cell lymphoma, especially those with relapsed or refractory disease.
Graphical abstract
The highly selective BTK inhibitor orelabrutinib has no significant effect on IL-2-inducible T cell kinase, which preserved the ADCC effects of rituximab induced by NK cells. The combination of orelabrutinib and rituximab will likely benefit patients with B cell malignant tumors, especially those with relapsed or refractory disease.
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Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma
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Autor/in / Beteiligte Person: | Zhu, Jun ; Li, Jiao ; Fang, Wei ; Wang, Xing ; Yu, Hui ; Song, Yuqin ; Ye, Yingying ; Mi, Lan ; Ding, Ning ; Wang, Xiaogan ; Wang, Dedao |
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Zeitschrift: | Molecular Therapy Oncolytics, Jg. 21 (2021-04-01), S. 158-170 |
Veröffentlichung: | American Society of Gene & Cell Therapy, 2021 |
Medientyp: | unknown |
ISSN: | 2372-7705 (print) |
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