RT Journal Article
SR Electronic
T1 Single-step Enzymatic Glycoengineering for the Construction of Antibody-cell Conjugates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 279240
DO 10.1101/279240
A1 Jie Li
A1 Mingkuan Chen
A1 Zilei Liu
A1 Linda Zhang
A1 Brunie H. Felding
A1 Gregoire Lauvau
A1 Michael Abadier
A1 Klaus Ley
A1 Peng Wu
YR 2018
UL http://biorxiv.org/content/early/2018/03/10/279240.abstract
AB 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 enzyme’s 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.