A Single-Step Chemoenzymatic Reaction for the Construction
of Antibody–Cell Conjugates
Version 3 2018-12-26, 05:20
Version 2 2018-12-07, 21:04
Version 1 2018-12-06, 21:46
Posted on 2018-12-26 - 05:20
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.
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Li, Jie; Chen, Mingkuan; Liu, Zilei; Zhang, Linda; Felding, Brunie H.; Moremen, Kelley W.; et al. (2018). A Single-Step Chemoenzymatic Reaction for the Construction
of Antibody–Cell Conjugates. ACS Publications. Collection. https://doi.org/10.1021/acscentsci.8b00552
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AUTHORS (10)
JL
Jie Li
MC
Mingkuan Chen
ZL
Zilei Liu
LZ
Linda Zhang
BF
Brunie H. Felding
KM
Kelley W. Moremen
GL
Gregoire Lauvau
MA
Michael Abadier
KL
Klaus Ley
PW
Peng Wu
KEYWORDS
transfer bio-macromoleculesresearch toolssubstrate tolerancecell lineskiller cell linehuman xenograft modelHerceptin-NK -92MI conjugatestumor cellsMWACCdonor substrate GDP-FucoseHERIgG antibodyKDcell modificationfuture drug discoverycell-surface engineeringSingle-Step Chemoenzymatic Reactionnovel functionalitieschemoenzymatic methodengineer cellschemoenzymatic approach