Adoptive T cell therapy (ACT) has emerged as a powerful strategy in cancer immunotherapy, with artificial antigen-presenting cells (aAPCs) serving as key mediators to enhance therapeutic efficacy. Protein-based materials are particularly advantageous for aAPCs because they combine molecular precision, dynamic flexibility, and intrinsic biocompatibility, allowing synthetic systems to closely recapitulate natural antigen–receptor interactions. We introduce globular protein vesicles (GPVs), self-assembled from recombinant fusion proteins incorporating monomeric streptavidin (mSA), as a proof-of-concept platform for programmable immune signaling. This modular architecture supports high-affinity, multivalent binding of biotinylated ligands, enabling precise control over receptor density and surface composition. GPVs exhibit excellent stability, mechanical resilience, and compatibility under physiological conditions, supporting in vitro T cell co-culture and activation studies. Furthermore, their dual functionality allows encapsulation of chemotherapeutic agents and controlled release under tumor-like conditions. Together, these findings establish mSA-GPVs as a versatile and scalable platform for engineering soft, functionalized vesicles with tunable ligand presentation and therapeutic payload delivery, advancing next-generation aAPC technologies to improve the efficacy of ACT.
