Antibody Dependent Cellular Cytotoxicity (ADCC) represents a major mode of tumoricidal action associated with a number of current immunotherapeutics such as monoclonal antibodies (mAbs). ADCC requires a minimum density of antibodies bound to the cancer cell to effectively cluster receptors such as CD16a on Natural Killer cells (NK). Receptor clustering activates NK cells to lyse the antibody coated cancer cell. As a result, a number of antibody-based immunotherapeutics are limited to destroying the small percentage of cancers associated with high tumor antigen/target receptor expression levels (&gt;&gt;104 /cell). We are working to develop a new tumor immunotherapeutic targeting technology based on Antibody Recruiting Polymers (ARPs). ARPs are substituted with multiple binding sites for both tumor antigens/target receptors and endogenous serum antibodies at optimized intra-polymer spacings, capable of recruiting high densities of immune machinery to cancer cell surfaces per receptor binding event. As such, ARPs can potentially promote antibody dependent immune responses against cancer cells with lower target receptor expression levels (103-104 /cell). ARPs can bind cancer cells with uniquely high avidity and selectivity (due to the multi-valent binding of multiple target receptors) resulting in a potent immune response and favorable kinetics of cancer cell elimination with minimal binding of non-cancer tissue. Additionally, ARPs can be tuned through the facile incorporation of different receptor binding ligands to target different cancer cell types, or different receptors on the same target surface using a single ARP molecule. This presentation will discuss the potential utility of ARPs in targeting cancer cells with fewer surface target receptors for ADCC, increasing the therapeutic window of antibody dependent immune responses by targeting a wider range of cells.

Antibody recruiting polymers as a tumor immunotherapeutic targeting strategy

256th National Meeting (2018)

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