Factor VIII T and B Cell Epitope Variants Having Reduced Immunogenicity
The researchers at Benaroya Research Institute and Puget Sound Blood Center have mapped immunogenic epitopes within FVIII and their variance capable of reducing inhibition by T- and B-cells. The minimal epitopes within FVIII capable of eliciting immune response mediated by T-cell and B-cell have been identified. In addition target residues for modification within the epitopes designed to reduce immunogenicity through decreased interaction with MHC class II and antibodies are available.
Blood coagulation is a multistep process involving blood platelets and various coagulation factors. Deficiency in functional coagulation Factor VIII (FVIII), one of the proteins essential to the process, results in Hemophilia A. Hemophilia A is an X-linked recessive hereditary bleeding disorder more prevalent in males. A third of the diagnosed cases are due to presence of de novo mutation. Standard treatment for hemophilia A is a replacement therapy using functional FVIII, episodically as treatment for bleeding and or in regular intervals to prevent uncontrolled bleeding. Unfortunately, inhibitory response against treatment FVIII occurs in 30% of patients with severe hemophilia A. In many cases the high titer of the inhibitory antibodies and their persistence renders infusion of Factor VIII ineffective, creating a need for less immunogenic treatments.
Incidence of hemophilia A in US is estimated to be 1 in 5000 males born. The incidence in males is estimated to be 5.2 times that of females. Hemophilia A market was $5.2 billion in 2011 and is expected to grow to $7 billion by 2016. Due to the chronic nature of the disease, gravity of illness, and high incidence of immunity developed against available therapeutics, development of effective FVIII treatment that prevents or reduces immunogenicity is beneficial.
Benaroya Research Institute and Puget Sound Blood Center are currently seeking U.S. patent protection for this technology.
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