Authors: Ariel Isser, Aliyah B. Silver, Hawley C. Pruitt, Michal Mass, Emma H. Elias, Gohta Aihara, Si-Sim Kang, Niklas Bachmann, Ying-Yu Chen, Elissa K. Leonard, Joan G. Bieler, Worarat Chaisawangwong, Joseph Choy, Sydney R. Shannon, Sharon Gerecht, Jeffrey S. Weber, Jamie B. Spangler, Jonathan P. Schneck
Published: 2022-10-14
DOI: 10.1038/s41467-022-33597-y
Source: Full article
AbstractHelper (CD4+) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8+) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4+T cells hinders consistency and scalability of CD4+ T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4+ T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules. When combined with soluble co-stimulation signals, MHC II artificial APCs (aAPCs) expand cognate murine CD4+T cells, including rare endogenous subsets, to induce potent effector functions in vitro and in vivo. Moreover, MHC II aAPCs provide help signals that enhance antitumor function of aAPC-activated CD8+T cells in a mouse tumor model. Lastly, human leukocyte antigen class II-based aAPCs expand rare subsets of functional, antigen-specific human CD4+T cells. Overall, MHC II aAPCs provide a promising approach for harnessing targeted CD4+ T cell responses.