B细胞定向治疗的新方法:超越利妥昔单抗。
New approaches of B-cell-directed therapy: beyond rituximab.
作者信息
Dörner Thomas, Burmester Gerd R
机构信息
Charite Center 14, Charite University Hospital Berlin, Berlin, Germany.
出版信息
Curr Opin Rheumatol. 2008 May;20(3):263-8. doi: 10.1097/BOR.0b013e3282f5e08d.
PURPOSE OF REVIEW
This study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity.
RECENT FINDINGS
Beyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported.
SUMMARY
The value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.
综述目的
本研究回顾了自身免疫性疾病中直接和间接靶向B细胞的治疗方法及其对保护性免疫的影响。
最新发现
除了近期利妥昔单抗作为B细胞耗竭剂的临床经验外,其他靶向CD20的生物制剂,如奥瑞珠单抗、奥法木单抗、hA20和TRU-015主要耗竭B细胞,目前正处于不同实体的临床研究中。此外,抗CD22靶向作为另一种已在临床试验中研究的方法,显示出适度的耗竭,但能抑制B细胞活化。更多间接的创新性影响B细胞的疗法包括细胞因子阻断,如B细胞活化因子(BAFF/BLyS)、增殖诱导配体(APRIL)及其受体,以及共刺激阻断。尽管观察到免疫球蛋白水平下降,但迄今为止尚未报告感染大幅增加。
总结
某些B细胞耗竭疗法以及其他调节B细胞功能的疗法的价值需要进一步明确,尤其是在类风湿关节炎、特定的胶原血管疾病和血管炎的治疗方案中。还需要对保护性免疫进行长期观察,以进一步评估感染率。