抗cd20细胞治疗多发性硬化症- Ocrelizumab的固定剂量计划是过度杀伤。

IF 2 Q3 PHARMACOLOGY & PHARMACY Drug Target Insights Pub Date : 2017-10-25 eCollection Date: 2017-01-01 DOI:10.1177/1177392817737515
Jagannadha Avasarala
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引用次数: 11

摘要

抗cd20疗法在多发性硬化症(MS)中有重要的应用。仅基于使用利妥昔单抗(RTX;Rituxan, Genentech和Biogen)在神经免疫疾病中的应用,ocrelizumab (OCR;Ocrevus(基因泰克公司)作为MS的治疗选择而开发,选择性靶向CD20 B细胞,这是一种存在于前B细胞、成熟B细胞和记忆B细胞上的细胞表面抗原,但不存在于淋巴样干细胞和浆细胞上。根据间接证据,消除B细胞的抗原提呈能力和抗原非特异性免疫功能似乎是抗cd20 B细胞疗法治疗效果的核心。一个重要的问题是——为什么药物需要在固定的时间间隔给药,而不是基于一个可测量的终点,比如跟踪外周CD20细胞计数?每6个月注射一次药物的科学有效性很小,特别是如果外周血中CD20细胞计数可以忽略不计。在这一分析中,一个案例是每月跟踪CD19细胞群作为CD20细胞的替代品,以指导OCR再给药参数,而不是遵循计划给药参数。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill.

Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

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来源期刊
Drug Target Insights
Drug Target Insights PHARMACOLOGY & PHARMACY-
CiteScore
2.70
自引率
0.00%
发文量
5
审稿时长
8 weeks
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