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bioRxiv · 10.1101/279240

Single-step Enzymatic Glycoengineering for the Construction of Antibody-cell Conjugates

Li, J.·Chen, M.·Liu, Z.·Zhang, L.·Felding, B. H.·Lauvau, G.·Abadier, M.·Ley, K.·Wu, P.
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Abstract

Employing live cells as therapeutics is a direction of future drug discovery. An easy and robust method to modify the surfaces of cells directly to incorporate novel functionalities is highly desirable. However, many current methods for cell-surface engineering interfere with cells endogenous properties. Here we report an enzymatic approach that enables the transfer of biomacromolecules, such as a full length IgG antibody, to the glycocalyx on the surfaces of live cells when the antibody is conjugated to the enzymes natural donor substrate GDP-fucose. This method is fast and biocompatible with little interference to cells endogenous functions. We applied this method to construct two antibody-cell conjugates (ACCs) using different immune cells, and the modified cells exhibited specific tumor targeting and resistance to inhibitory signals produced by tumor cells, respectively. Remarkably, Herceptin-NK-92MI conjugates exhibits enhanced activities to induce the lysis of HER2+ cancer cells both ex vivo and in a murine tumor model, indicating its potential for further development as a clinical candidate.

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Li, J., Chen, M., Liu, Z., Zhang, L., Felding, B. H., Lauvau, G., Abadier, M., Ley, K., Wu, P.. 2018-03-10. Single-step Enzymatic Glycoengineering for the Construction of Antibody-cell Conjugates. https://doi.org/10.1101/279240

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