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Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082047/ https://www.ncbi.nlm.nih.gov/pubmed/33981831 http://dx.doi.org/10.1016/j.omto.2021.03.015 |
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author | Yu, Hui Wang, Xing Li, Jiao Ye, Yingying Wang, Dedao Fang, Wei Mi, Lan Ding, Ning Wang, Xiaogan Song, Yuqin Zhu, Jun |
author_facet | Yu, Hui Wang, Xing Li, Jiao Ye, Yingying Wang, Dedao Fang, Wei Mi, Lan Ding, Ning Wang, Xiaogan Song, Yuqin Zhu, Jun |
author_sort | Yu, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8082047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-80820472021-05-11 Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma Yu, Hui Wang, Xing Li, Jiao Ye, Yingying Wang, Dedao Fang, Wei Mi, Lan Ding, Ning Wang, Xiaogan Song, Yuqin Zhu, Jun Mol Ther Oncolytics Original Article 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. American Society of Gene & Cell Therapy 2021-04-03 /pmc/articles/PMC8082047/ /pubmed/33981831 http://dx.doi.org/10.1016/j.omto.2021.03.015 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yu, Hui Wang, Xing Li, Jiao Ye, Yingying Wang, Dedao Fang, Wei Mi, Lan Ding, Ning Wang, Xiaogan Song, Yuqin Zhu, Jun Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title | Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title_full | Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title_fullStr | Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title_full_unstemmed | Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title_short | Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma |
title_sort | addition of btk inhibitor orelabrutinib to rituximab improved anti-tumor effects in b cell lymphoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082047/ https://www.ncbi.nlm.nih.gov/pubmed/33981831 http://dx.doi.org/10.1016/j.omto.2021.03.015 |
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