Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy

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

Research output: Contribution to journalArticlepeer-review


Helper (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.

Original languageEnglish (US)
Article number6086
JournalNature communications
Issue number1
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General
  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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