Ing Mathieu, Gupta Nimesh, Teyssandier Maud, Maillère Bernard, Pallardy Marc, Delignat Sandrine, Lacroix-Desmazes Sébastien
Sorbonne Universités, Université Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Sorbonne Paris Cité, Université Paris Descartes, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France.
National Institute of Immunology, New Delhi, India.
Cell Immunol. 2016 Mar;301:40-8. doi: 10.1016/j.cellimm.2015.12.006. Epub 2015 Dec 19.
Replacement therapy for patients with hemophilia A using plasma-derived or recombinant factor VIII (FVIII) is complicated by the short half-life of the FVIII products and by the occurrence of neutralizing antibodies in a substantial number of patients. In the recent years, enormous efforts have been invested to develop new generations of coagulation factors with extended half-lives. Presumably, the use of long-lasting FVIII products should reduce the frequency of administration to the patients and drastically improve their quality of life. The question of their immunogenicity remains however unanswered as yet. The present review proposes a summary of the different strategies developed to enhance the half-life of FVIII, including fusion of FVIII to the Fc fragment of the human IgG1 or to human serum albumin, or attachment of polyethylene glycol. Based on the available literature, we hypothesize on the potential benefits or risks associated with each of the latter strategies in terms of immunogenicity of the newly derived hemostatic drugs.
使用血浆源性或重组凝血因子VIII（FVIII）对甲型血友病患者进行替代治疗，因FVIII产品半衰期短以及大量患者出现中和抗体而变得复杂。近年来，人们投入了巨大努力来开发新一代半衰期延长的凝血因子。据推测，使用长效FVIII产品应能减少给患者给药的频率，并大幅改善他们的生活质量。然而，它们的免疫原性问题仍未得到解答。本综述总结了为延长FVIII半衰期而开发的不同策略，包括将FVIII与人IgG1的Fc片段或人血清白蛋白融合，或连接聚乙二醇。基于现有文献，我们推测了后述每种策略在新衍生止血药物免疫原性方面的潜在益处或风险。
