A Single-Step Chemoenzymatic Reaction for the Construction of Antibody-Cell Conjugates

Jie Li, Mingkuan Chen, Zilei Liu, Linda Zhang, Brunie H. Felding, Kelley W. Moremen, Gregoire Lauvau, Michael Abadier, Klaus Ley, Peng Wu

Research output: Contribution to journalArticle

4 Scopus citations

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, genetic methods for cell-surface engineering are laborious and limited by low efficiency for primary cell modification. Here we report a chemoenzymatic approach that exploits a fucosyltransferase to transfer bio-macromolecules, such as an IgG antibody (MW∼ 150 KD), to the glycocalyx on the surfaces of live cells when the antibody is conjugated to the enzyme's natural donor substrate GDP-Fucose. Requiring no genetic modification, 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 both cell lines and primary cells, and the modified cells exhibited specific tumor targeting and resistance to inhibitory signals produced by tumor cells, respectively. Remarkably, Herceptin-NK-92MI conjugates, a natural killer cell line modified with Herceptin, exhibit enhanced activities to induce the lysis of HER2+ cancer cells both ex vivo and in a human tumor xenograft model. Given the unprecedented substrate tolerance of the fucosyltransferase, this chemoenzymatic method offers a general approach to engineer cells as research tools and for therapeutic applications.

Original languageEnglish (US)
Pages (from-to)1633-1641
Number of pages9
JournalACS Central Science
Volume4
Issue number12
DOIs
StatePublished - Dec 26 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Li, J., Chen, M., Liu, Z., Zhang, L., Felding, B. H., Moremen, K. W., Lauvau, G., Abadier, M., Ley, K., & Wu, P. (2018). A Single-Step Chemoenzymatic Reaction for the Construction of Antibody-Cell Conjugates. ACS Central Science, 4(12), 1633-1641. https://doi.org/10.1021/acscentsci.8b00552