期刊
CELLULAR IMMUNOLOGY
卷 301, 期 -, 页码 40-48出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2015.12.006
关键词
Hemophilia; Coagulation factor; Factor VIII; Long-lasting; Immunogenicity; Fc fusion; Albumin fusion; PEGylation
资金
- Institut national de la sante et de la recherche medicale (Inserm)
- Centre National de la Recherche Scientifique (CNRS)
- Universite Pierre et Marie Curie (UPMC) Paris 6
- Innovative Medicines Initiative Joint Undertaking [115303]
- Ministere de l'enseignement superieur et de la recherche (France)
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. (C) 2015 Elsevier Inc. All rights reserved.
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