文摘
客观的描述nipocalimab的影响,一个完整的人,effectorless IgG1 anti-neonatal Fc受体(FcRn)单克隆抗体免疫功能。
背景Nipocalimab FcRn高亲和力结合防止免疫球蛋白回收,导致降低血清免疫球蛋白总量,包括致病性免疫球蛋白自身抗体。快速、持续降低的免疫球蛋白g观察第二阶段活泼研究广义重症肌无力(gMG)和在第一阶段健康志愿者。gMG病人,nipocalimab诱导快速和持续降低anti-AChR自身抗体和MG-ADL分数,但没有严重不良事件包括临床上重要的感染。
设计/方法Nipocalimab广泛评估在体外和非人primate-based慢性毒理研究评估选择性,耐受性、安全性和免疫药理学。安全性、耐受性和immune-focused评估在临床研究阶段1和阶段2毫克也完成(NCT02828046,NCT03772587)。
结果Nipocalimab结合具体体外FcRn没有激活的效应函数或抑制抗原表达。在非人灵长类动物管理高达300毫克/公斤nipocalimab QW长达6个月,观察持续降低的免疫球蛋白g没有不利影响。Immunotoxicology确认不影响免疫细胞表型;CD8 T细胞、NK或固有细胞功能;T-dependent neoantigen IgM反应。观察Neoantigen免疫球蛋白生产,但降低了峰值免疫球蛋白浓度符合预期的增加免疫球蛋白与nipocalimab间隙。在临床研究中,nipocalimab证明可再生的选择性降低总血清免疫球蛋白,包括所有免疫球蛋白的子类,对IgM没有影响,IgA, IgE, CH50、C3、C4、炎性细胞因子或急性期蛋白,包括c反应蛋白(CRP)。
结论这些数据表明,nipocalimab可以选择性地降低免疫球蛋白g和免疫球蛋白自身抗体,同时保留细胞免疫,完成IgM后反应和免疫球蛋白生产neoantigen挑战。总的来说,nipocalimab的选择性影响免疫球蛋白回收提供了一个机械的理由可能降低感染风险,尽管大量的免疫球蛋白降低。
脚注
披露:凌博士获得了个人作为一个雇员补偿詹森制药(强生)。凌医生詹森制药(强生公司)的股票。凌博士收到发现或技术知识产权利益有关卫生保健。凌博士收到发现或技术知识产权利益有关卫生保健。泰勒先生曾获得个人赔偿AVROBIO作为一个员工,INC . Beneduce先生收到了个人作为一个雇员补偿詹森强生制药。Beneduce先生曾获得股票或所有权从詹森强生制药。Beneduce先生收到发现或技术知识产权利益有关卫生保健。余女士已经收到个人赔偿作为詹森制药的员工。余女士已经收到个人赔偿作为动量制药的员工。余女士已经在强生股票。 Dr. Brown has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Dr. Brown has received personal compensation for serving as an employee of Momenta Pharmaceuticals. Dr. Brown has received stock or an ownership interest from Janssen Pharmaceuticals. Dr. Brown has received stock or an ownership interest from Momenta Pharmaceuticals. Dr. Brown has received intellectual property interests from a discovery or technology relating to health care. Dr. Kumar has received personal compensation for serving as an employee of GlaxoSmithKline. Dr. Kumar has received personal compensation for serving as an employee of Checkmate Pharmaceuticals. Dr. Kumar has received stock or an ownership interest from GSK. Dr. Kumar has received stock or an ownership interest from Checkmate Pharmaceuticals. Dr. Xu has nothing to disclose. Dr. Duffner has received personal compensation for activities with Momenta Pharmaceuticals. Dr. Avery has received personal compensation for serving as an employee of Lyndra Therapeutics. Dr. Avery has received personal compensation for serving as an employee of Xilio Therapeutics. Dr. Avery has received personal compensation for serving as an employee of Kisbee Therapeutics. Dr. Avery has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta Pharmaceutical. Dr. Avery has received stock or an ownership interest from Life Biosciences.
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