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 and Jonathan P. Schneck ()
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Ariel Isser: Johns Hopkins University School of Medicine
Aliyah B. Silver: Johns Hopkins University School of Medicine
Hawley C. Pruitt: Johns Hopkins University Whiting School of Engineering
Michal Mass: Johns Hopkins University School of Medicine
Emma H. Elias: Johns Hopkins University Krieger School of Arts and Sciences
Gohta Aihara: Johns Hopkins University School of Medicine
Si-Sim Kang: Johns Hopkins University School of Medicine
Niklas Bachmann: Johns Hopkins University School of Medicine
Ying-Yu Chen: Johns Hopkins University School of Medicine
Elissa K. Leonard: Johns Hopkins University School of Medicine
Joan G. Bieler: Johns Hopkins University School of Medicine
Worarat Chaisawangwong: Johns Hopkins University School of Medicine
Joseph Choy: Johns Hopkins University School of Medicine
Sydney R. Shannon: Johns Hopkins University School of Medicine
Sharon Gerecht: Johns Hopkins University School of Medicine
Jeffrey S. Weber: NYU Langone Health
Jamie B. Spangler: Johns Hopkins University School of Medicine
Jonathan P. Schneck: Johns Hopkins University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-33597-y

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