Cell surface clicking of antibody-recruiting polymers to metabolically azide-labeled cancer cells

Uvyn, Annemiek; Coen, Ruben De; Wever, Olivier De; Deswarte, Kim; Lambrecht, Bart N.; Geest, Bruno G. De

doi:10.1039/c9cc03379c

Cited by 26 publications

(32 citation statements)

References 15 publications

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“…In this regard, bioorthogonal click reactions are an attractive alternative [9] . Moreover, the ease by which azides can be introduced onto a cell surface through metabolic labeling with azido sugars allows for introducing a high density of synthetic low molecular weight cell surface receptors with a reported minimal influence on the cellular functionality [10–12] . Azides immediately prompt the combination with strained cycloalkynes as complimentary reaction partners to form a stable triazole bond through the efficient and highly bioorthogonal strain‐promoted azide‐alkyne cycloaddition (SPAAC) reaction [10] .…”

Section: Methodsmentioning

confidence: 99%

Covalent Cell Surface Conjugation of Nanoparticles by a Combination of Metabolic Labeling and Click Chemistry

et al. 2021

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Conjugation of nanoparticles (NP) to the surface of living cells is of interest in the context of exploiting the tissue homing properties of ex vivo engineered T cells for tumor‐targeted delivery of drugs loaded into NP. Cell surface conjugation requires either a covalent or non‐covalent reaction. Non‐covalent conjugation with ligand‐decorated NP (LNP) is challenging and involves a dynamic equilibrium between the bound and unbound state. Covalent NP conjugation results in a permanently bound state of NP, but the current routes for cell surface conjugation face slow reaction kinetics and random conjugation to proteins in the glycocalyx. To address the unmet need for alternative bioorthogonal strategies that allow for efficient covalent cell surface conjugation, we developed a 2‐step click conjugation sequence in which cells are first metabolically labeled with azides followed by reaction with sulfo‐6‐methyl‐tetrazine‐dibenzyl cyclooctyne (Tz‐DBCO) by SPAAC, and subsequent IEDDA with trans‐cyclooctene (TCO) functionalized NP. In contrast to using only metabolic azide labeling and subsequent conjugation of DBCO‐NP, our 2‐step method yields a highly specific cell surface conjugation of LNP, with very low non‐specific background binding.

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Section: Methodsmentioning

confidence: 99%

Covalent Cell Surface Conjugation of Nanoparticles by a Combination of Metabolic Labeling and Click Chemistry

et al. 2021

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“…In vitro analysis showed that only polymers containing both DBCO and DNP were capable to recruit antibodies to an azide‐labeled cancer cell surface in 2D and 3D cell cultures (Figure 8). [65] It is also interesting to note that very recently the Rullo group has reported on antibody recruiting molecules that were able to covalently conjugate to endogenous antibodies through proximity driven ligation [44] which could also open up interesting avenues when translated to macromolecular antibody recruiting entities.…”

Section: Multivalent Antibody‐recruiting Macromoleculesmentioning

confidence: 99%

Multivalent Antibody‐Recruiting Macromolecules: Linking Increased Binding Affinity with Enhanced Innate Immune Killing

Uvyn

Geest

2020

ChemBioChem

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Antibody-recruiting molecules (ARMs) are a novel class of immunotherapeutics. They are capable of introducing antibodies onto disease-relevant targets such as cancer cells, bacterial cells or viruses. This can induce antibody-mediated immune responses such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent phagocytosis (ADCP), which can kill the pathogen. In contrast to the classic ARMs, multivalent ARMs could offer the advantage of increasing the efficiency of antibody recruitment and subsequent innate immune killing. Such compounds consist of multiple target-binding termini (TBT) and/or antibody-binding termini (ABT). Those multivalent interactions are able to convert low binding affinities into increased binding avidities. This minireview summarizes the current status of multivalent ARMs and gives insight into possible benefits, hurdles still to be overcome and future perspectives.

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“…The introduction of bio‐orthogonal azide groups using metabolic glycan labeling has also been used to engineer live cells, through introduction of Ac 4 ManNAz, with antibody‐recruiting polymers (ARPs). [ 75 ] For this purpose, pentafluorophenyl acrylate (PFPA) polymers functionalized with an octyl alkyne were introduced in Jurkat cells and used to immobilize anti‐2,4‐dinitrophenyl (DNP) antibodies on the cell surface (Figure 4C,D). [ 76 ] This concept was further extended to mouse 4T1 spheroids, demonstrating good penetration into the azide‐labeled spheroids and binding to the surface of individual cells.…”

Section: Covalent Conjugation Using Bio‐orthogonal Chemistrymentioning

confidence: 99%

Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications

Arno

2020

Macromol. Rapid Commun.

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Manipulating the surface of living cells represents a powerful tool by which to control cell behavior and provides a unique strategy to modulate cellular function and cell–cell interactions. Recent progress in this area has seen the development of robust and elegant approaches to selectively decorate the cell surface, leading to unprecedented advances in cellular manipulation and cell‐based therapies. Despite some impressive in vitro results, several obstacles remain to the broader application of some of these strategies, including their limited translation in vivo. In this review, the leading techniques used to introduce polymers at the plasma membrane of mammalian cells are discussed, focusing on strategies that generate a stable and homogeneous distribution of polymeric chains at the cell surface. Application of these strategies to control cell behavior and deliver cell‐based therapies to targeted tissues are highlighted.

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Cell surface clicking of antibody-recruiting polymers to metabolically azide-labeled cancer cells

Abstract: Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue.

Cited by 26 publications

References 15 publications

Covalent Cell Surface Conjugation of Nanoparticles by a Combination of Metabolic Labeling and Click Chemistry

Covalent Cell Surface Conjugation of Nanoparticles by a Combination of Metabolic Labeling and Click Chemistry

Multivalent Antibody‐Recruiting Macromolecules: Linking Increased Binding Affinity with Enhanced Innate Immune Killing

Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications

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