[Rinshō ketsueki] The Japanese journal of clinical hematology
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Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. ⋯ The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.
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Chimeric antigen receptor (CAR) is the generic name for synthetic T cell receptors redirected to tumor-associated antigens. Most CARs consist of an ectodomain (scFv or ligand), a hinge region, a transmembrane domain, and signaling endodomains derived from one or two co-stimulatory molecules (CD28, 4-1BB, etc) and from a CD3-ζ chain. CD19-targeted CAR T cell therapy has achieved major success in the treatment of B cell malignancies. ⋯ CD19 CAR T cell therapy from allogeneic donors including third party donors is a potential option for B-cell malignancies. CAR T cell therapies for myeloma, acute myeloid leukemia, and T-cell leukemia are still under development. Our group is currently preparing a phase I study of CD19 CAR T cell therapy in pediatric and young adult patients with ALL using a non-viral gene transfer method, the piggyBac-transposon system.