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Cell Immunol. 2016 Mar;301:40-8. doi: 10.1016/j.cellimm.2015.12.006. Epub 2015 Dec 19.

Immunogenicity of long-lasting recombinant factor VIII products.

Author information

1
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.
2
National Institute of Immunology, New Delhi, India.
3
CEA-Saclay Institute of Biology and Technologies, Gif sur Yvette, France.
4
INSERM, UMR996, Faculté Pharmacie, Université Paris Sud, France.
5
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. Electronic address: sebastien.lacroix-desmazes@crc.jussieu.fr.

Abstract

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.

KEYWORDS:

Albumin fusion; Coagulation factor; Factor VIII; Fc fusion; Hemophilia; Immunogenicity; Long-lasting; PEGylation

PMID:
26723503
DOI:
10.1016/j.cellimm.2015.12.006
[Indexed for MEDLINE]

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