Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.

PURPOSE OF REVIEW: Prenatal stem cell and gene therapy approaches are amongst the few therapies that can promise the birth of a healthy infant with specific known genetic diseases. This review describes fetal immune cell signaling and its potential influence on donor cell engraftment, and summarizes mechanisms of central T cell tolerance to peripherally-acquired antigen in the context of prenatal therapies for Hemophilia A.

RECENT FINDINGS: During early gestation, different subsets of antigen presenting cells take up peripherally-acquired, non-inherited antigens and induce the deletion of antigen-reactive T-cell precursors in the thymus, demonstrating the potential for using prenatal cell and gene therapies to induce central tolerance to FVIII in the context of prenatal diagnosis/therapy of Hemophilia A.

SUMMARY: Prenatal cell and gene therapies are promising approaches to treat several genetic disorders including Hemophilia A and B. Understanding the mechanisms of how FVIII-specific tolerance is achieved during ontogeny could help develop novel therapies for HA and better approaches to overcome FVIII inhibitors.