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抗 MAdCAM 单克隆抗体治疗 IBD 的合理临床开发。

Rational and clinical development of the anti-MAdCAM monoclonal antibody for the treatment of IBD.

机构信息

a Inflammatory Bowel Disease Center and Amsterdam Gastroenterology and Metabolism , Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.

出版信息

Expert Opin Biol Ther. 2019 Apr;19(4):361-366. doi: 10.1080/14712598.2019.1576631. Epub 2019 Feb 11.

Abstract

INTRODUCTION

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in gut-associated lymphoid tissue is upregulated in patients with inflammatory bowel disease (IBD). Blocking adhesion molecules and thereby inhibiting migration of lymphocytes into sites of inflammation in the gut is an attractive new treatment target in drug development for IBD.

AREAS COVERED

This review discusses the preclinical and clinical experience on SHP647 (previously called PF-00547659 and PF-00547,659), a fully human IgG2K monoclonal antibody that binds to MAdCAM-1 to selectively reduce lymphocyte homing to the intestinal tract.

EXPERT OPINION

Blocking endothelial adhesion molecule MAdCAM-1 could represent an attractive target for the treatment of IBD. In the next years, the results from the phase III studies as well as data to support therapeutic drug monitoring based on drug levels to guide and optimize individual therapy will become available. Furthermore, much effort is put in the development of clinical prediction models to predict which drug is optimal for an individual patient.

摘要

简介

黏附分子细胞黏附分子-1(MAdCAM-1)在肠道相关淋巴组织中的表达在炎症性肠病(IBD)患者中上调。阻断黏附分子,从而抑制淋巴细胞迁移到肠道炎症部位,这是开发用于 IBD 的药物的一个有吸引力的新治疗靶点。

涵盖领域

这篇综述讨论了 SHP647(以前称为 PF-00547659 和 PF-00547,659)的临床前和临床经验,SHP647 是一种全人源 IgG2K 单克隆抗体,可与 MAdCAM-1 结合,选择性减少淋巴细胞向肠道的归巢。

专家意见

阻断内皮细胞黏附分子 MAdCAM-1 可能是治疗 IBD 的一个有吸引力的靶点。在未来几年,III 期研究结果以及支持基于药物水平进行治疗药物监测以指导和优化个体化治疗的数据将可用。此外,还投入了大量精力开发临床预测模型,以预测哪种药物对个体患者最佳。

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