VHH antibody targeting the chemokine receptor CX3CR1 inhibits progression of atherosclerosis

被引：36

作者：

Low, Sarah ^{[1
]}

Wu, Haixia ^{[1
]}

Jerath, Kavita ^{[1
,5
]}

Tibolla, Annette ^{[2
]}

Fogal, Birgit ^{[2
]}

Conrad, Rebecca ^{[2
]}

MacDougall, Margit ^{[2
,6
]}

Kerr, Steven ^{[2
]}

Berger, Valentina ^{[2
]}

Dave, Rajvee ^{[2
]}

Villalona, Jorge ^{[2
]}

Pantages, Lynn ^{[2
]}

Ahlberg, Jennifer ^{[3
]}

Li, Hua ^{[3
]}

Van Hoorick, Diane ^{[4
,10
]}

Ververken, Cedric ^{[4
,7
]}

Broadwater, John ^{[2
]}

Waterman, Alisa ^{[2
,8
]}

Singh, Sanjaya ^{[1
,9
]}

Kroe-Barrett, Rachel ^{[1
]}

机构：

[1] Boehringer Ingelhe Pharmaceut Inc, Biotherapeut Mol Discovery, 900 Ridgebury Rd, Ridgefield, CT 06877 USA

[2] Boehringer Ingelhe Pharmaceut Inc, Cardiometab Dis Res, Ridgefield, CT 06877 USA

[3] Boehringer Ingelhe Pharmaceut Inc, Biotherapeut Pharmacokinet, Ridgefield, CT 06877 USA

[4] Ablynx Sanofi Co, Project Management, Zwijnaarde, Belgium

[5] Merck, West Point, PA USA

[6] Vascumab LLC, Branford, CT USA

[7] Confo Therapeut NV, Technol Pk 94, B-9052 Ghent, Belgium

[8] FreeThink Technol Inc, Branford, CT USA

[9] Janssen Pharmaceut, Spring House, PA USA

[10] eTheRNA, Niel, Belgium

来源：

MABS | 2020年 / 12卷 / 01期

关键词：

VHH Antibodies; GPCR; atherosclerosis; BI; 655088; biophysical assessment; pharmacokinetic profile; humanization; FRACTALKINE; IDENTIFICATION; FRAGMENTS; BINDING; DISEASE;

D O I：

10.1080/19420862.2019.1709322

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

CX3CR1 has been identified as a highly attractive target for several therapeutic interventions. Despite this potential, no potent antagonists, either small molecule or monoclonal antibody, have been identified. Here we describe the lead finding and engineering approach that lead to the identification of BI 655088, a potent biotherapeutic antagonist to CX3CR1. BI 655088 is a potent CX3CR1 antagonist that, upon therapeutic dosing, significantly inhibits plaque progression in the standard mouse model of atherosclerosis. BI 655088 represents a novel and highly selective biotherapeutic that could reduce inflammation in the atherosclerotic plaque when added to standard of care treatment including statins, which could result in a significant decrease in atherothrombotic events in patients with existing cardiovascular disease.

引用

页数：12

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