Protein-only Nanoparticles for T Cell Expansion and Activation

Abstract

The in vitro expansion and activation of T cells utilizing synthetic nanosized artificial antigen presenting cells (aAPCs) have emerged as a promising technique for cancer treatment. Although diverse nanomaterials have been explored as aAPC scaffolds, protein-only nanoparticles have been largely overlooked, despite their high designability and biocompatibility. In this study, we exploit a plug-and-play approach for the development of protein-only nanoparticles as aAPCs using the self-assembling properties of ZapB coiled coil and the Z-domain antibody-capturing ability. The resulting coiled coil-based nanoparticles (ccNPs) can be easily, rapidly, and simultaneously functionalized with anti-CD3 and anti-CD28 antibodies (ccNPs-CD3/CD28). Our results demonstrate that ccNPs-CD3/CD28 induce polyclonal T cell proliferation and activation while sustaining cytokine production for an extended period. The biocompatibility, modularity, and chemistry-free surface modification of this protein-only strategy render it a versatile platform for in vitro T cell expansion and activation.