Polysaccharide hydrogels as immunologically active vaccine depots for cancer immunotherapy

Cancer vaccines aim to elicit durable, antigen-specific antitumour immunity, yet clinical translation remains constrained by inefficient antigen retention, weak innate immune activation, and poor spatiotemporal coordination of immune priming. Biomaterial-based vaccine depots, particularly hydrogels incorporating natural polysaccharides, can address these barriers by creating immune-instructive microenvironments that support localised and sustained antigen delivery. Polysaccharide-based hydrogels combine structural support, tuneable release kinetics, and intrinsic immunomodulatory properties through direct engagement with antigen-presenting cells. This review analyses their development as cancer vaccine depots. Alginate-based cryogels and microporous scaffolds are discussed as platforms that promote antigen-presenting cell recruitment, activation, and prolonged local antigen presentation, supporting durable adaptive responses. Hyaluronic acid hydrogels, deployed as injectable or implantable systems, are highlighted for sustaining antigen delivery and modulating the tumor-immune interface to limit recurrence. Hybrid platforms combining alginate or hyaluronic acid with synthetic polymers, proteins, or immunostimulatory cargos are examined as strategies to optimize mechanics, release, and immunogenicity. Emerging polysaccharides, including chitosan, fucoidan, pullulan, mannan, dextran, β-glucans, and cellulose derivatives, are evaluated as immunomodulatory components, despite more limited validation in cancer vaccination. Finally, translational challenges related to reproducibility, sterilization, scalability, and regulation are discussed, defining a framework for clinically relevant hydrogel vaccine depots.