Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside.
Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside.
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DOI：
10.1097/bor.0b013e328344c15e
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发表时间：
2011-05
影响因子：
5.1
通讯作者：
Cancro MP
中科院分区：
文献类型：
--
作者：
Stohl W;Scholz JL;Cancro MP
BLyS家族配体和受体是大多数成熟B淋巴细胞的选择和存活的关键参与者。BLyS在过渡B细胞选择中的基本作用，加上记忆B细胞和浆细胞的相对BLyS独立性，表明BLyS可能是针对免疫前B细胞池的策略中的有用的治疗靶标。几种靶向BLyS的药物目前正在进行临床试验，我们在这里总结了最近的结果，重点是系统性红斑狼疮（SLE）。贝利木单抗是一种人类中和抗BLyS单克隆抗体，在两项独立的系统性红斑狼疮（SLE）III期临床试验中获得了中度但阳性的结果，最近被FDA顾问小组推荐批准。靶向BLyS或该细胞因子受体家族其他成员的其他药物也正在临床试验中进行测试。总之，这些试验应该为一种使人衰弱且往往难以治愈的疾病提供新的疗法;并提供见解，反过来又应该促进下一代风湿性疾病的个性化靶向疗法。
BLyS family ligands and receptors are key players in the selection and survival of most mature B lymphocytes. The fundamental role of BLyS in transitional B cell selection, coupled with the relative BLyS-independence of memory B cells and plasma cells, suggests that BLyS may be a useful therapeutic target in strategies directed against pre-immune B cell pools. Several agents that target BLyS are in clinical trials now, and we summarize recent results here, with a focus on systemic lupus erythematosus (SLE). Belimumab, a human neutralizing anti-BLyS monoclonal antibody, has delivered moderate but positive results in two separate phase III clinical trials for systemic lupus erythematosus (SLE), and was recently recommended for approval by an FDA advisory panel. Additional agents targeting BLyS or other members of this cytokine receptor family are also being tested in clinical trials. Together, these trials should yield novel therapies for a debilitating and often intractable illness; and offer insights that in turn should foster subsequent generations of personalized, targeted therapies for rheumatic diseases.