Narimatsu, Y. | bioRxiv Science

bioRxiv2020

Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy

CD22, a member of Siglec family of sialic acid binding proteins, has restricted expression on B cells. Antibody-based agents targeting CD22 or CD20 (Rituxan) on B lymphoma and leukemia cells exhibit clinical efficacy for treating these malignancies, but also attack normal B cells leading to immune deficiency. Here, we report a chemoenzymatic glycocalyx editing strategy to introduce high-affinity and specific CD22 ligands onto NK-92MI and cytokine-induced killer (CIK) cells to achieve tumor-specific CD22 targeting. These CD22-ligand modified cells exhibited significantly enhanced tumor cell binding and killing in vitro without harming healthy B cells. For effective lymphoma cell killing in vivo we further functionalized CD22 ligand-modified NK-92MI cells with the E-selectin ligand sialyl Lewis X to promote trafficking to bone marrow. The cells containing the ligands of both CD22 and selectins resulted in the efficient suppression of B lymphoma in a xenograft model. Our results suggest that NK cells modified with glycan ligands to CD22 and selectins promote both targeted killing of B lymphoma cells and improved trafficking to sites where the cancer cells reside, respectively.

bioengineering↗

bioRxiv2020

Estimating maximum sustainable yield of snow crab (Chionoecetes opilio) off Tohoku Japan via a state-space assessment model with time-varying natural mortality

Yield from fisheries is a tangible benefit of ecosystem services and sustaining or restoring a fish stock level to achieve a maximum sustainable yield (MSY). Snow crab (Chionoecetes opilio) off Tohoku has been managed by a total allowable catch since 1996, although their abundance has not increased even after 2011, when fishing pressure rapidly decreased because of the Great East Japan Earthquake. This implies that their biological characteristics, such as recruits, natural mortality coefficient (M), and terminal molting probabilities (p), might have changed. We developed "just another state-space stock assessment model (JASAM)" to estimate the MSY of the snow crab off Tohoku, Japan, considering interannual variations in M and p. The multi-model inference revealed that M increased from 0.2 in 1997 to 0.59 in 2018, although it was not different among the instars, sex, nor terminal molt of crabs. The parameter p also increased by 1.34-2.46 times depending on the instar growth stages from 1997 to 2018. We estimated the MSYs in three scenarios, which drastically changed if M and p were set as they were in the past or at the current values estimated from this study. This result indicated that the MSY of snow crab would also be time-varying based on their time-varying biological characteristics.

ecology↗