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

Author

Listed:
  • Ariel Isser

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Aliyah B. Silver

    (Johns Hopkins University School of Medicine
    Johns Hopkins University Bloomberg School of Public Health
    Johns Hopkins University School of Medicine)

  • Hawley C. Pruitt

    (Johns Hopkins University Whiting School of Engineering
    Johns Hopkins University Whiting School of Engineering)

  • Michal Mass

    (Johns Hopkins University School of Medicine
    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
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Joan G. Bieler

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Worarat Chaisawangwong

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Joseph Choy

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University Whiting School of Engineering
    Johns Hopkins University Whiting School of Engineering)

  • Sydney R. Shannon

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Sharon Gerecht

    (Johns Hopkins University School of Medicine
    Johns Hopkins University Whiting School of Engineering
    Johns Hopkins University Whiting School of Engineering
    Johns Hopkins University Whiting School of Engineering)

  • Jeffrey S. Weber

    (NYU Langone Health)

  • Jamie B. Spangler

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University Whiting School of Engineering
    Johns Hopkins University Whiting School of Engineering)

  • Jonathan P. Schneck

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

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.

Suggested Citation

  • 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 Chaisawangw, 2022. "Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33597-y
    DOI: 10.1038/s41467-022-33597-y
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    References listed on IDEAS

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