autologous CD34+ peripheral blood stem cells expressing B-domain deleted Factor VIII

Autologous CD34+ peripheral blood stem cells expressing B-domain deleted Factor VIII (Pleightlet) is an investigational autologous stem cell gene therapy developed by the Medical College of Wisconsin for the treatment of severe hemophilia A, particularly in patients with high-titer inhibitors. The therapy involves the ex vivo transduction of a patient's own CD34+ hematopoietic stem cells with a lentiviral vector encoding a B-domain deleted form of human coagulation Factor VIII (BDDFVIII). The expression of BDDFVIII is controlled by the platelet-specific ITGA2B (GPIIb) promoter, ensuring that the protein is synthesized and sequestered within the alpha-granules of megakaryocytes and their derivative platelets. Upon re-infusion, these engineered cells provide a localized source of FVIII that is released directly at sites of vascular injury during platelet activation, potentially shielding the factor from circulating neutralizing antibodies (inhibitors) and restoring hemostatic function.

Brand names

Pleightlet

Other names

Platelet-Targeted FVIII Gene Therapyautologous CD34+ PBSCs expressing BDDFVIII