A Structurally Dynamic Pathogen-Mimicking Biomaterial Is an Efficient Activator of Dendritic Cells.

Structural dynamism confers intriguing applications to biocompatible materials. Here, we present a protein-based, self-organizing microscale material designed to mimic pathogen-like features. In this formulation, the building block proteins shift their organization through monomeric, microscale, or oligomeric nanoscale states, which is expected to enhance antigen uptake and immune activation. To validate the system, several CT26-derived tumor neoantigens, namely, Ubqln1, AHSL and Phf3, have been assembled as mixed granules, leaking nanoscale protein oligomers. When challenging dendritic cells, this formulation enhanced the expression of the activation markers CD40 and MHC II compared with soluble antigens, underscoring the material's ability to potentiate antigen-presenting functions. While many antigens are attractive targets due to their unique expression in malignant cells, their poor immunogenicity in soluble versions may render them ineffective. The present approach represents a transversal and feasible tool to enhance the immunogenicity of protein antigens through a dynamic material platform that expands their translational potential.