Customizable Glycopolymers as Adjuvants for Cancer Immunotherapy: From Branching Degree Optimization to Cell Surface Engineering

Engineering dendritic cell (DC) maturation is paramount for robust T-cell responses and immunological memory, critical for cancer immunotherapy. This work unveils a novel strategy using precisely controlled branching in synthetic glycopolymers to optimize DC activation. Using the distinct copolymerization kinetics of 2-(methacrylamido) glucopyranose (MAG) and diethylene glycol dimethacrylate (DEGDMA) in a RAFT polymerization, unique glycopolymers with varying branching degrees are created. These strategically produced gradient branched glycopolymers with sugar moieties on the outer chain potently promote DC maturation. Strikingly, low-branched glycopolymers demonstrate superior activity, both in pure form and when engineered on tumor cell surfaces. Quartz crystal microbalance and theoretical simulations elucidate the crucial role of branching in modulating glycopolymer-DC receptor interactions. Low-branched gradient glycopolymers have shown a notable advantage and are promising adjuvants in DC-based cancer immunotherapy.