FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity

Author:

Ettinger Ruth A.12,Liberman Joseph A.1,Gunasekera Devi13,Puranik Komal1,James Eddie A.2ORCID,Thompson Arthur R.14,Pratt Kathleen P.134ORCID

Affiliation:

1. Bloodworks Northwest Research Institute, Seattle, WA;

2. Benaroya Research Institute, Seattle, WA;

3. Uniformed Services University of the Health Sciences, Bethesda, MD; and

4. Division of Hematology, Department Medicine, University of Washington, Seattle, WA

Abstract

Key Points Less immunogenic FVIII muteins were designed by defining and replacing MHCII anchor residues with amino acids that reduced MHCII binding. Patient-derived T-cell clones show lower proliferation in response to FVIII-F2196K, which had normal FVIII activity and expression level.

Publisher

American Society of Hematology

Subject

Hematology

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