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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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    1. J. Joseph Melenhorst & Gregory M. Chen & Meng Wang & David L. Porter & Changya Chen & McKensie A. Collins & Peng Gao & Shovik Bandyopadhyay & Hongxing Sun & Ziran Zhao & Stefan Lundh & Iulian Pruteanu, 2022. "Decade-long leukaemia remissions with persistence of CD4+ CAR T cells," Nature, Nature, vol. 602(7897), pages 503-509, February.
    2. Xavier Clemente-Casares & Jesus Blanco & Poornima Ambalavanan & Jun Yamanouchi & Santiswarup Singha & Cesar Fandos & Sue Tsai & Jinguo Wang & Nahir Garabatos & Cristina Izquierdo & Smriti Agrawal & Mi, 2016. "Expanding antigen-specific regulatory networks to treat autoimmunity," Nature, Nature, vol. 530(7591), pages 434-440, February.
    3. Elise Alspach & Danielle M. Lussier & Alexander P. Miceli & Ilya Kizhvatov & Michel DuPage & Adrienne M. Luoma & Wei Meng & Cheryl F. Lichti & Ekaterina Esaulova & Anthony N. Vomund & Daniele Runci & , 2019. "MHC-II neoantigens shape tumour immunity and response to immunotherapy," Nature, Nature, vol. 574(7780), pages 696-701, October.
    4. Sebastian Kreiter & Mathias Vormehr & Niels van de Roemer & Mustafa Diken & Martin Löwer & Jan Diekmann & Sebastian Boegel & Barbara Schrörs & Fulvia Vascotto & John C. Castle & Arbel D. Tadmor & Step, 2015. "Erratum: Mutant MHC class II epitopes drive therapeutic immune responses to cancer," Nature, Nature, vol. 523(7560), pages 370-370, July.
    5. Sebastian Kreiter & Mathias Vormehr & Niels van de Roemer & Mustafa Diken & Martin Löwer & Jan Diekmann & Sebastian Boegel & Barbara Schrörs & Fulvia Vascotto & John C. Castle & Arbel D. Tadmor & Step, 2015. "Mutant MHC class II epitopes drive therapeutic immune responses to cancer," Nature, Nature, vol. 520(7549), pages 692-696, April.
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