BTK Inhibitor Ibrutinib Reduces Bispecific Antibody-Related CRS Without Undermining the Anti-Tumor Efficacy.
4 affiliations
- 1Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
- 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
- 3Department of Health Care, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing, China.
- 4ITabMed Ltd., Shanghai, China.
Abstract
Bispecific antibodies (BsAbs) have shown marked efficacy in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, their clinical utility is constrained by cytokine release syndrome (CRS). Therefore, identification of strategies to mitigate CRS without compromising the antitumor activity of BsAbs is important. This study aimed to investigate the characteristics of CRS in BsAb therapies and identify effective intervention approaches. Analysis of serum cytokine profiles from patients receiving BsAbs revealed that IL-6, IL-8, and IL-10 levels were markedly elevated at CRS onset. Our results, together with public data, suggested that monocytes/macrophages served as the primary sources of these cytokines. In vitro experiments confirmed that the presence of macrophages substantially enhanced BsAb-induced cytokine production. In vivo macrophage depletion attenuates CRS-related cytokine release, underscoring the central role of macrophages in BsAb-induced CRS. Furthermore, in vitro experiments and in vivo humanized models have shown that bruton's tyrosine kinase (BTK) inhibitors modulate macrophage phenotype and reduce the production of IL-6, IL-8, and IL-10 without impairing the therapeutic efficacy of BsAbs. Collectively, BTK inhibitors can reduce key cytokine production in CRS by regulating the phenotype of BsAb activated macrophages, potentially lowering CRS risk and severity during BsAb therapy.
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BibTeX
@article{cao2026inhibitor,
title = {{BTK Inhibitor Ibrutinib Reduces Bispecific Antibody-Related CRS Without Undermining the Anti-Tumor Efficacy.}},
author = {Jiaowu Cao and Dingyao Hu and Jie Lv and Jin Chai and Yue Wang and Jie Chen and Xiaoqiang Yan and Jun Zhu and Hui Yu},
journal = {Cancer science},
year = {2026},
month = oct,
doi = {10.1111/cas.70575},
url = {https://europepmc.org/article/MED/42952196},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - BTK Inhibitor Ibrutinib Reduces Bispecific Antibody-Related CRS Without Undermining the Anti-Tumor Efficacy.
AU - Jiaowu Cao
AU - Dingyao Hu
AU - Jie Lv
AU - Jin Chai
AU - Yue Wang
AU - Jie Chen
AU - Xiaoqiang Yan
AU - Jun Zhu
AU - Hui Yu
PY - 2026
DA - 2026/10/28
JO - Cancer science
DO - 10.1111/cas.70575
UR - https://europepmc.org/article/MED/42952196
AB - Bispecific antibodies (BsAbs) have shown marked efficacy in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, their clinical utility is constrained by cytokine release syndrome (CRS). Therefore, identification of strategies to mitigate CRS without compromising the antitumor activity of BsAbs is important. This study aimed to investigate the characteristics of CRS in BsAb therapies and identify effective intervention approaches. Analysis of serum cytokine profiles from patients receiving BsAbs revealed that IL-6, IL-8, and IL-10 levels were markedly elevated at CRS onset. Our results, together with public data, suggested that monocytes/macrophages served as the primary sources of these cytokines. In vitro experiments confirmed that the presence of macrophages substantially enhanced BsAb-induced cytokine production. In vivo macrophage depletion attenuates CRS-related cytokine release, underscoring the central role of macrophages in BsAb-induced CRS. Furthermore, in vitro experiments and in vivo humanized models have shown that bruton's tyrosine kinase (BTK) inhibitors modulate macrophage phenotype and reduce the production of IL-6, IL-8, and IL-10 without impairing the therapeutic efficacy of BsAbs. Collectively, BTK inhibitors can reduce key cytokine production in CRS by regulating the phenotype of BsAb activated macrophages, potentially lowering CRS risk and severity during BsAb therapy.
SN - 1347-9032
SN - 1349-7006
ER -