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

Overview

Journal ACS Cent Sci

Specialty Chemistry

Date 2019 Jan 17

PMID 30648147

Citations 29

Authors

Jie Li

Mingkuan Chen

Zilei Liu

Linda Zhang

Brunie H Felding

Kelley W Moremen

Gregoire Lauvau

Michael Abadier

Klaus Ley

Peng Wu

Affiliations

Soon will be listed here.

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 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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References

Tornoe C, Christensen C, Meldal M . Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem. 2002; 67(9):3057-64. DOI: 10.1021/jo011148j. View

Shearer R, Saunders D . Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives. Genes Cells. 2014; 20(1):1-10. DOI: 10.1111/gtc.12183. View

Griffin M, Hsieh-Wilson L . Glycan Engineering for Cell and Developmental Biology. Cell Chem Biol. 2016; 23(1):108-121. PMC: 4857608. DOI: 10.1016/j.chembiol.2015.12.007. View

Cornetta K, Pollok K, Miller A . Transduction of primary hematopoietic cells by retroviral vectors. CSH Protoc. 2011; 2008:pdb.prot4884. DOI: 10.1101/pdb.prot4884. View

Stephan M, Irvine D . Enhancing Cell therapies from the Outside In: Cell Surface Engineering Using Synthetic Nanomaterials. Nano Today. 2011; 6(3):309-325. PMC: 3148657. DOI: 10.1016/j.nantod.2011.04.001. View

Schonfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M . Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther. 2014; 23(2):330-8. PMC: 4445620. DOI: 10.1038/mt.2014.219. View

Munn D, Bronte V . Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol. 2015; 39:1-6. PMC: 5627973. DOI: 10.1016/j.coi.2015.10.009. View

Swartz M, Hirosue S, Hubbell J . Engineering approaches to immunotherapy. Sci Transl Med. 2012; 4(148):148rv9. DOI: 10.1126/scitranslmed.3003763. View

Oliveira B, Guo Z, Bernardes G . Inverse electron demand Diels-Alder reactions in chemical biology. Chem Soc Rev. 2017; 46(16):4895-4950. DOI: 10.1039/c7cs00184c. View

10.

Hudak J, Bertozzi C . Glycotherapy: new advances inspire a reemergence of glycans in medicine. Chem Biol. 2013; 21(1):16-37. PMC: 4111574. DOI: 10.1016/j.chembiol.2013.09.010. View

11.

Bi X, Yin J, Chen Guanbang A, Liu C . Chemical and Enzymatic Strategies for Bacterial and Mammalian Cell Surface Engineering. Chemistry. 2018; 24(32):8042-8050. DOI: 10.1002/chem.201705049. View

12.

Besanceney-Webler C, Jiang H, Zheng T, Feng L, Del Amo D, Wang W . Increasing the efficacy of bioorthogonal click reactions for bioconjugation: a comparative study. Angew Chem Int Ed Engl. 2011; 50(35):8051-6. PMC: 3465470. DOI: 10.1002/anie.201101817. View

13.

Srivastava G, Kaur K, Hindsgaul O, Palcic M . Enzymatic transfer of a preassembled trisaccharide antigen to cell surfaces using a fucosyltransferase. J Biol Chem. 1992; 267(31):22356-61. View

14.

Rahim M, Kota R, Haun J . Enhancing reactivity for bioorthogonal pretargeting by unmasking antibody-conjugated trans-cyclooctenes. Bioconjug Chem. 2015; 26(2):352-60. PMC: 5022565. DOI: 10.1021/bc500605g. View

15.

Prasad V . Immunotherapy: Tisagenlecleucel - the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol. 2017; 15(1):11-12. DOI: 10.1038/nrclinonc.2017.156. View

16.

Shi P, Ju E, Yan Z, Gao N, Wang J, Hou J . Spatiotemporal control of cell-cell reversible interactions using molecular engineering. Nat Commun. 2016; 7:13088. PMC: 5059747. DOI: 10.1038/ncomms13088. View

17.

Giorgi M, Agusti R, de Lederkremer R . Carbohydrate PEGylation, an approach to improve pharmacological potency. Beilstein J Org Chem. 2014; 10:1433-44. PMC: 4077506. DOI: 10.3762/bjoc.10.147. View

18.

Selvaraj R, Fox J . trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling. Curr Opin Chem Biol. 2013; 17(5):753-60. PMC: 3925366. DOI: 10.1016/j.cbpa.2013.07.031. View

19.

Stephan M, Moon J, Um S, Bershteyn A, Irvine D . Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med. 2010; 16(9):1035-41. PMC: 2935928. DOI: 10.1038/nm.2198. View

20.

Rostovtsev V, Green L, Fokin V, Sharpless K . A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew Chem Int Ed Engl. 2002; 41(14):2596-9. DOI: 10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4. View