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

Autor: Isser A; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Silver AB; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Pruitt HC; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA., Mass M; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Elias EH; Department of Biology, Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD, 21287, USA., Aihara G; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Kang SS; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Bachmann N; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Chen YY; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Leonard EK; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Bieler JG; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Chaisawangwong W; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Choy J; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA., Shannon SR; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Gerecht S; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Weber JS; Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, 10016, USA., Spangler JB; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Schneck JP; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 14; Vol. 13 (1), pp. 6086. Date of Electronic Publication: 2022 Oct 14.
DOI: 10.1038/s41467-022-33597-y
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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