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

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Biocompatible materials with structural dynamism offer unique applications.
• Developing materials that mimic pathogen features can enhance immune responses.
• Protein-based materials present a versatile platform for biomedical applications.

Purpose of the Study:

• To create a self-organizing, protein-based microscale material mimicking pathogen-like features.
• To investigate the material's ability to enhance antigen uptake and immune activation.
• To improve the immunogenicity of tumor neoantigens for potential cancer immunotherapy.

Main Methods:

• Formulation of a protein-based material with dynamic structural states (monomeric, microscale, oligomeric nanoscale).
• Assembly of CT26-derived tumor neoantigens (Ubqln1, AHSL, Phf3) into mixed granules.
• Challenging dendritic cells with the formulated antigens and assessing activation markers (CD40, MHC II).

Main Results:

• The protein material demonstrated self-organization into different structural states.
• Formulated neoantigens enhanced dendritic cell expression of CD40 and MHC II compared to soluble antigens.
• The material effectively potentiated antigen-presenting cell functions.

Conclusions:

• The dynamic protein material platform enhances the immunogenicity of protein antigens.
• This approach offers a feasible method to improve the translational potential of antigens for immunotherapy.
• Mimicking pathogen features with dynamic biomaterials is a promising strategy for immune activation.