-
Natural sciences
- Synthesis of materials
- Medicinal and biomolecular chemistry not elsewhere classified
-
Medical and health sciences
- Adaptive immunology
- Innate immunity
Recognition of the tail region of monoclonal antibodies by immune cells is a potent trigger of anti-cancer activity. However, this requires the presence of a known protein on the surface of a cancer cell. Hence, there is an unmet need for strategies that can unleash the power of innate immune killing to kill cancer cells that lack a suitable cell surface signature. Recently, we introduced the concept of antibody recruiting polymers which are polymers that bind to the cell surface and contain multiple motifs that bind to endogenous antibodies. Endogenous antibodies are antibodies against specific small molecule haptens that are prevalent in human serum. We have shown that multivalent polymers containing multiple haptens induce potent killing of cancer cells. The overarching goal of the present project is to investigate whether such cancer cell killing can be linked to the induction of immunological memory which would allow the immune system to recognize and eliminate cancer cells at distal metastatic location. To address this question, we will design Janus Antibody-recruiting Macromolecules (JAMs). JAMs are well-defined dendritic that contain multiple antibody-recruiting motifs and multiple cell surface binding motifs. Using JAMs, we will explore several strategies for optimal cancer cell surface targeting of antibody recruiting motifs to induce cancer cell killing with concomitant delivery of immune-activation stimuli to tumor-specific immunity.