Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary; SeroScience Ltd., Budapest, Hungary.
MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
Nanomedicine. 2016 May;12(4):1023-1031. doi: 10.1016/j.nano.2015.11.019. Epub 2015 Dec 28.
Hypersensitivity reactions to particulate drugs can partly be caused by complement activation and represent a major complication during intravenous application of nanomedicines. Several liposomal and micellar drugs and carriers, and therapeutic antibodies, were shown to activate complement and induce complement activation-related pseudoallergy (CARPA) in model animals. To explore the possible use of the natural complement inhibitor factor H (FH) against CARPA, we examined the effect of FH on complement activation induced by CARPAgenic drugs. Exogenous FH inhibited complement activation induced by the antifungal liposomal Amphotericin-B (AmBisome), the widely used solvent of anticancer drugs Cremophor EL, and the anticancer monoclonal antibody rituximab in vitro. An engineered form of FH (mini-FH) was more potent inhibitor of Ambisome-, Cremophor EL- and rituximab-induced complement activation than FH. The FH-related protein CFHR1 had no inhibitory effect. Our data suggest that FH or its derivatives may be considered in the pharmacological prevention of CARPA.
Although liposomes and micelles are already in use in the clinical setting as drug carriers, there remains the potential problem of hypersensitivity due to complement activation. In this article, the authors investigated the use of complement inhibitor factor H (FH) on complement activation and showed good efficacy. The results would therefore suggest the potential application of complement inhibitor in the future.
颗粒药物的过敏反应部分可由补体激活引起，并且是静脉内应用纳米药物时的主要并发症。几种脂质体和胶束药物和载体以及治疗性抗体已被证明可在模型动物中激活补体并引起补体激活相关假性过敏反应（CARPA）。为了探讨天然补体抑制剂因子 H（FH）对 CARPA 的可能用途，我们研究了 FH 对 CARPA 性药物诱导的补体激活的影响。外源性 FH 抑制了体外抗真菌脂质体两性霉素 B（AmBisome）、广泛用于抗癌药物 Cremophor EL 的溶剂以及抗癌单克隆抗体利妥昔单抗诱导的补体激活。FH 的一种工程形式（mini-FH）比 FH 更能抑制 Ambisome、Cremophor EL 和 rituximab 诱导的补体激活。与 FH 相关的蛋白 CFHR1 没有抑制作用。我们的数据表明，FH 或其衍生物可能被考虑用于预防 CARPA。
尽管脂质体和胶束已经作为药物载体在临床环境中使用，但由于补体激活，仍存在过敏反应的潜在问题。在这篇文章中，作者研究了补体抑制剂因子 H（FH）对补体激活的作用，并显示出良好的疗效。因此，这些结果表明在未来可能应用补体抑制剂。
