Insights from in vitro global assays on possible doses of concomitant hemostatic agents in the presence of NXT007 in hemophilia A.

Background: Concomitant administration of activated prothrombin complex concentrate (APCC) at doses >100 U/kg/d is associated with thrombotic risk under emicizumab prophylaxis. In vitro global assay data on the effects of concomitant coagulation factor agents in the presence of NXT007, an emicizumab-based engineered bispecific antibody under clinical development, may serve as a basis for addressing this potential risk.

Objectives: This study aimed to investigate the in vitro effects of recombinant factor (rF)VIII, rFVIIa, and APCC during NXT007 treatment and estimate tolerable doses with reference to emicizumab.

NXT007-mediated hemostatic potential is suppressed by activated protein C-catalyzed inactivation of activated factor V.

Background: Activated protein C (APC) inactivates activated factor (F) V (FVa) and FVIIIa. NXT007, an emicizumab-based engineered therapeutic bispecific antibody, enhances the coagulation potential of FVIII-deficient plasma (FVIIIdef-plasma) to near normal levels. However, little is known about the effect of APC-induced inactivation in NXT007-mediated hemostatic function.

Complete Biosynthetic Pathway of the Phosphonate Phosphonothrixin: Two Distinct Thiamine Diphosphate-Dependent Enzymes Divide the Work to Form a C-C Bond.

Phosphonates often exhibit biological activities by mimicking the phosphates and carboxylates of biological molecules. The phosphonate phosphonothrixin (PTX), produced by the soil-dwelling bacterium sp. ST-888, exhibits herbicidal activity.

Dual Roles of PU.1 in the Expression of PD-L2: Direct Transactivation with IRF4 and Indirect Epigenetic Regulation.

PD-L2, which has been identified as a PD-1 ligand, is specifically expressed in dendritic cells (DCs) and macrophages. The transcription factors that determine the cell type-specific expression of PD-L2 are largely unknown, although PD-1 and its ligands, which have been shown to play important roles in T cell suppression, have been vigorously analyzed in the field of cancer immunology. To reveal the mechanism by which gene expression is regulated, we focused on DCs, which play key roles in innate and acquired immunity.