Suppr超能文献

一种针对白细胞介素 6 受体和白细胞介素 17A 的双特异性抗体,用于治疗自身免疫性和炎症性疾病患者的潜在疗法。

A bispecific antibody that targets IL-6 receptor and IL-17A for the potential therapy of patients with autoimmune and inflammatory diseases.

机构信息

From Tanabe Research Labs U.S.A. Inc., San Diego, California 92121 and.

Covagen AG, Wagistrasse 25, 8952 Schlieren, Switzerland.

出版信息

J Biol Chem. 2018 Jun 15;293(24):9326-9334. doi: 10.1074/jbc.M117.818559. Epub 2018 Apr 20.

Abstract

Despite the success of current biological therapeutics for rheumatoid arthritis, these therapies, targeting individual cytokines or pathways, produce beneficial responses in only about half of patients. Therefore, better therapeutics are needed. IL-6 and IL-17A are proinflammatory cytokines in many autoimmune and inflammatory diseases, and several therapeutics have been developed to specifically inhibit them. However, targeting both of these cytokines with a bispecific therapeutic agent could account for their nonoverlapping proinflammatory functions and for the fact that IL-6 and IL-17A act in a positive feedback loop. Here, we present the development of MT-6194, a bispecific antibody targeting both IL-6R and IL-17A that was developed with the FynomAb technology. We also present data from mouse inflammatory disease experiments, indicating that simultaneous inhibition of both IL-6 and IL-17A yields enhanced efficacy compared with inhibition of each cytokine alone.

摘要

尽管目前针对类风湿关节炎的生物疗法取得了成功,但这些针对单个细胞因子或途径的疗法仅能使约一半的患者受益。因此,需要更好的治疗方法。IL-6 和 IL-17A 是许多自身免疫性和炎症性疾病中的促炎细胞因子,已经开发出几种治疗方法来专门抑制它们。然而,使用双特异性治疗剂同时靶向这两种细胞因子可以解释它们非重叠的促炎功能,以及 IL-6 和 IL-17A 以正反馈环的方式起作用。在这里,我们介绍了 MT-6194 的开发,这是一种针对 IL-6R 和 IL-17A 的双特异性抗体,是使用 FynomAb 技术开发的。我们还提供了来自小鼠炎症性疾病实验的数据,表明同时抑制 IL-6 和 IL-17A 比单独抑制每种细胞因子产生更高的疗效。

相似文献

4
Development of tibulizumab, a tetravalent bispecific antibody targeting BAFF and IL-17A for the treatment of autoimmune disease.
MAbs. 2019 Aug/Sep;11(6):1175-1190. doi: 10.1080/19420862.2019.1624463. Epub 2019 Jun 10.
6
Discovery and preclinical evaluation of KYS202004A, a novel bispecific fusion protein targeting TNF-α and IL-17A, in autoimmune disease models.
Int Immunopharmacol. 2024 Jul 30;136:112383. doi: 10.1016/j.intimp.2024.112383. Epub 2024 Jun 5.
9
Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases.
FEBS Lett. 2011 Dec 1;585(23):3699-709. doi: 10.1016/j.febslet.2011.03.023. Epub 2011 Mar 21.

引用本文的文献

1
Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.
Signal Transduct Target Ther. 2024 Oct 4;9(1):263. doi: 10.1038/s41392-024-01952-8.
2
Targeting IL-6 trans-signalling: past, present and future prospects.
Nat Rev Immunol. 2023 Oct;23(10):666-681. doi: 10.1038/s41577-023-00856-y. Epub 2023 Apr 17.
3
Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics.
Clin Immunol. 2023 Jan;246:109201. doi: 10.1016/j.clim.2022.109201. Epub 2022 Dec 5.
5
The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury.
J Inflamm Res. 2022 Nov 18;15:6357-6371. doi: 10.2147/JIR.S384279. eCollection 2022.
6
Bioassay Development for Bispecific Antibodies-Challenges and Opportunities.
Int J Mol Sci. 2021 May 19;22(10):5350. doi: 10.3390/ijms22105350.
7
A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target.
Front Immunol. 2020 Oct 2;11:539797. doi: 10.3389/fimmu.2020.539797. eCollection 2020.
8
Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective.
J Exp Med. 2020 Jan 6;217(1). doi: 10.1084/jem.20191123.
9
Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow.
Mol Ther Oncolytics. 2019 Mar 23;14:38-56. doi: 10.1016/j.omto.2019.02.004. eCollection 2019 Sep 27.
10
Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma.
Front Endocrinol (Lausanne). 2019 Jan 8;9:788. doi: 10.3389/fendo.2018.00788. eCollection 2018.

本文引用的文献

1
Despite slow progress, bispecifics generate buzz.
Nat Biotechnol. 2016 Dec 7;34(12):1215-1217. doi: 10.1038/nbt1216-1215.
3
Immunogenicity of tocilizumab in patients with rheumatoid arthritis.
Joint Bone Spine. 2017 Jan;84(1):39-45. doi: 10.1016/j.jbspin.2016.04.013. Epub 2016 Jun 28.
5
The IL-23-IL-17 axis in inflammatory arthritis.
Nat Rev Rheumatol. 2015 Jul;11(7):415-29. doi: 10.1038/nrrheum.2015.53. Epub 2015 Apr 28.
6
Interleukin 17A acts synergistically with interferon γ to promote protection against Leishmania infantum infection.
J Infect Dis. 2015 Mar 15;211(6):1015-26. doi: 10.1093/infdis/jiu531. Epub 2014 Oct 1.
7
IL-6 in inflammation, immunity, and disease.
Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295. doi: 10.1101/cshperspect.a016295.
8
A bispecific HER2-targeting FynomAb with superior antitumor activity and novel mode of action.
Mol Cancer Ther. 2014 Aug;13(8):2030-9. doi: 10.1158/1535-7163.MCT-14-0046-T. Epub 2014 Jul 3.
9
Interleukin 6 and rheumatoid arthritis.
Biomed Res Int. 2014;2014:698313. doi: 10.1155/2014/698313. Epub 2014 Jan 12.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验