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Tolerance induction in hemophilia: innovation and accomplishments.
Current Opinion in Hematology 2018 September
PURPOSE OF REVIEW: Hemophilia is an X-linked blood coagulation genetic disorder, which can cause significant disability. Replacement therapy for coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) may result in the development of high-affinity alloantibodies ('inhibitors') to the replacement therapy, thus making it ineffective. Therefore, there is interest in directing immunological responses towards tolerance to infused factors.
RECENT FINDINGS: In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of current tolerance induction protocols (ITI), preclinical and clinical data of pharmacological immune modulation, hepatic gene therapy, and the rapidly advancing field of cell therapies. We will also evaluate publications reporting data from preclinical studies on oral tolerance induction using chloroplast-transgenic (transplastomic) plants.
SUMMARY: Until now, no clinical prophylactic immune modulatory protocol exists to prevent inhibitor formation to infused clotting factors. Recent innovative technologies provide hope for improved eradication and perhaps even prevention of inhibitors.
RECENT FINDINGS: In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of current tolerance induction protocols (ITI), preclinical and clinical data of pharmacological immune modulation, hepatic gene therapy, and the rapidly advancing field of cell therapies. We will also evaluate publications reporting data from preclinical studies on oral tolerance induction using chloroplast-transgenic (transplastomic) plants.
SUMMARY: Until now, no clinical prophylactic immune modulatory protocol exists to prevent inhibitor formation to infused clotting factors. Recent innovative technologies provide hope for improved eradication and perhaps even prevention of inhibitors.
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