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

Hong, S.; Yu, C.; Wang, P.; Shi, Y.; Cheng, B.; CHEN, M.; Chapla, D. G.; Reigh, N.; Narimatsu, Y.; Chen, X.; Clausen, H.; Moremen, K. W.; Macauley, M. S.; Paulson, J. C.; Wu, P.

doi:10.1101/2020.03.23.004325

bioRxiv · 10.1101/2020.03.23.004325

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

Hong, S.·Yu, C.·Wang, P.·Shi, Y.·Cheng, B.·CHEN, M.·Chapla, D. G.·Reigh, N.·Narimatsu, Y.·Chen, X.·Clausen, H.·Moremen, K. W.·Macauley, M. S.·Paulson, J. C.·Wu, P.

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Abstract

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.

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Hong, S., Yu, C., Wang, P., Shi, Y., Cheng, B., CHEN, M., Chapla, D. G., Reigh, N., Narimatsu, Y., Chen, X., Clausen, H., Moremen, K. W., Macauley, M. S., Paulson, J. C., Wu, P.. 2020-03-25. Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy. https://doi.org/10.1101/2020.03.23.004325

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