F.SM07.04.11 Engineering innate immune-mediated cancer cell killing by antibody recruiting macromolecules
Annemiek Uvyn, Ghent University
Antibody therapy focuses on targeting antibodies onto the surface of cancer cells by innate immune mechanisms such as complement activation, antibody-dependent cell-mediated cytotoxicity, or antibody-dependent cellular phagocytosis to induce cancer cell killing. Monoclonal antibody therapy is limited in its high cost and side effects. And the research work lead by Annemiek Uvyn, from Ghent University, suggests that using synthetic systems that can recruit endogenous antibodies onto cancer cell surfaces can be a viable alternative for antibody therapy.
The research group works on developing antibody-recruiting polymers that can be used for cancer immunotherapy. These antibody recruiting polymers contain a target binding domain (to bind to the cell surface ) and an antibody binding domain (to bind to the antibody F-ab region). They can be injected directly into tumors to induce their attachment to cancer cell surfaces at one end and covalently attach the endogenous antibodies at the other. This binding would thus recruit immune cell-mediated cancer killing.
Interestingly, Annemiek says that a lipid anchor inserted into the phospholipid cell membrane is being used to covalently conjugate to the glycocalyx of metabolically azido-labeled cells. And azido-labelling becomes crucial to enhance the binding efficiency of antibody recruiting polymers (DBCO or DNP polymers) on to the cells. In vitro analysis of the polymers with cancers showed that a dialkyl group lipid polymer attached to cancer cells could high efficiently recruit anti-DNP into the cell surface. Eventually, the polymer conjugated cancer cell killing efficiency was visualized with macrophages to show phagocytosis is being activated with the lipid polymers. This approach of developing antibody-recruiting polymers can revolutionize monoclonal antibody cancer immunotherapy.
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