Discovery of a novel Igß and FcγRIIB cross-linking antibody, ASP2713, and its potential application in the treatment of systemic lupus erythematosus.

B cell-targeted therapies have evolved as established therapies for systemic lupus erythematosus (SLE); however, existing approaches still do not thoroughly satisfy clinical requirements due to limited efficacy against memory B cells, autoantibody-producing plasmablasts and disease heterogeneity. To provide a new treatment option for SLE, we created a novel anti-Igß antibody with enhanced affinity for Fc gamma receptor (FcγR) IIB called ASP2713. ASP2713 cross-reacted with both human and cynomolgus monkey Igß and showed increased binding affinity for human and monkey FcγRIIB compared to native human IgG1. This binding property allows dominant B cell binding and induction of intrinsic negative feedback signals. In human B cells, ASP2713 significantly and concentration-dependently induced FcγRIIB ITIM phosphorylation, while suppressing proliferation under B cell receptor stimulation. This pharmacological effect was also confirmed in in vitro B cell proliferation and antibody production assays using peripheral B cells isolated from patients with SLE. In a cynomolgus monkey tetanus toxoid-induced antibody production model, ASP2713 almost completely inhibited the increase in antigen-specific antibodies with superior efficacy to rituximab. Additionally, ASP2713 significantly suppressed recall antibody production in response to secondary tetanus toxoid immunization, indicating the memory B cell- and plasmablast-targeting potential of ASP2713. Our results suggest that ASP2713 may have therapeutic potential as a treatment for SLE, where B cells play a pathogenic role.

Proposal for optimal placement platform of bikes using queueing networks.

In recent social experiments, rental motorbikes and rental bicycles have been arranged at nodes, and environments where users can ride these bikes have been improved. When people borrow bikes, they return them to nearby nodes. Some experiments have been conducted using the models of Hamachari of Yokohama, the Niigata Rental Cycle, and Bicing. However, from these experiments, the effectiveness of distributing bikes was unclear, and many models were discontinued midway. Thus, we need to consider whether these models are effectively designed to represent the distribution system. Therefore, we construct a model to arrange the nodes for distributing bikes using a queueing network. To adopt realistic values for our model, we use the Google Maps application program interface. Thus, we can easily obtain values of distance and transit time between nodes in various places in the world. Moreover, we apply the distribution of a population to a gravity model and we compute the effective transition probability for this queueing network. If the arrangement of the nodes and number of bikes at each node is known, we can precisely design the system. We illustrate our system using convenience stores as nodes and optimize the node configuration. As a result, we can optimize simultaneously the number of nodes, node places, and number of bikes for each node, and we can construct a base for a rental cycle business to use our system.