Symposium SM04/SM01: Beyond Nano-Challenges and Opportunities in Drug Delivery / Materials Modulating Stem Cells and Immune Response
Annemiek Uvyn, Ghent University
Tagging the Cancer Cell Surface for Innate Immune Recognition and Destruction by Bifunctional Multivalent Antibody-Recruiting Polymers
Written by Jessalyn Hui Ying Low
Monoclonal antibody (mAb) therapies are immunotherapies commonly used in cancer treatment to kill cancer cells, but have several limitations such as high production costs and possible severe side effects. “Instead of delivering mAB, synthetic compounds that can deliver endogenous antibodies to the cancer cell surface could be a viable alternative,” says Annemiek Uvyn, where Uvyn describes in this talk how antibody-recruiting polymers could be designed for this purpose.
Uvyn explains that these antibody-recruiting polymers are functionalized with two key classes of motifs—cell-binding motifs to bind to the cancer cell, as well as antibody-recruiting motifs to bind to the endogenous antibodies. Cell-binding motifs can be in the form of lipid motifs, for anchoring to the phospholipid bilayer of the cell membrane via hydrophobic interaction, or cyclooctyne motifs, for click coupling to azides introduced in the glycocalyx of cancer cells. As for antibody-recruiting motifs, haptens like dinitrophenyl (DNP) are used. It was also demonstrated that the more DNP units there are on the polymer backbone, the greater the binding avidity of antibodies.
With these antibody-recruiting polymers, it was validated successfully in vitro the ability for high avidity antibody binding and recruitment of antibodies to the cancer cells. More importantly, functional assay studies successfully showed that these lipid-polyDNP antibody-recruiting polymers could induce cancer cell killing via phagocytosis by macrophages, which was in fact achieved to a similar extent as that of cetuximab, a mAb. This highlights the potential of using these antibody-recruiting polymers for immunotherapies, to induce innate immune effector killing of cancer cells.