Efficient Innate Immune Killing of Cancer Cells Triggered by Cell‐Surface Anchoring of Multivalent Antibody‐Recruiting Polymers

Binding of monoclonal antibodies (mAbs) onto a cell surface triggers antibody‐mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs, synthetic systems that can recruit endogenous antibodies from the blood stream to a cancer cell surface could be of...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-09, Vol.58 (37), p.12988-12993
Main Authors: Uvyn, Annemiek, De Coen, Ruben, Gruijs, Mandy, Tuk, Cees W., De Vrieze, Jana, van Egmond, Marjolein, De Geest, Bruno G.
Format: Article
Language:English
Subjects:
Anchoring
antibodies
Avidity
Binding
Cancer
Cell activation
Cell membranes
Cell surface
Complement activation
Immune system
immune therapy
Immunotherapy
Inserts
Lipids
Macrophages
Monoclonal antibodies
multivalency
Phagocytosis
Phospholipids
polymer amphiphiles
Polymers
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Summary:Binding of monoclonal antibodies (mAbs) onto a cell surface triggers antibody‐mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs, synthetic systems that can recruit endogenous antibodies from the blood stream to a cancer cell surface could be of great relevance. Herein, we explore antibody‐recruiting polymers (ARPs) as a novel class of immunotherapy. ARPs consist of a cell‐binding motif linked to a polymer that contains multiple small molecule antibody‐binding motifs along its backbone. As a proof of concept, we employ a lipid anchor that inserts into the phospholipid cell membrane and make use of a polymeric activated ester scaffold onto which we substitute dinitrophenol as an antibody‐binding motif. We demonstrate that ARPs allow for high avidity antibody binding and drive antibody recruitment to treated cells for several days. Furthermore, we show that ARP‐treated cancer cells are prone to antibody‐mediated killing through phagocytosis by macrophages. Marked for death: Antibody‐recruiting polymers (ARPs), which consist of a cell‐binding motif linked to a polymer that contains multiple small molecule antibody‐binding motifs along its backbone, have been used to mark cancer cells for destruction by the innate immune system.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201905093