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Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines

Author

Listed:
  • Rimsha Bhatta

    (University of Illinois at Urbana-Champaign)

  • Joonsu Han

    (University of Illinois at Urbana-Champaign)

  • Yusheng Liu

    (University of Illinois at Urbana-Champaign)

  • Yang Bo

    (University of Illinois at Urbana-Champaign)

  • David Lee

    (University of Illinois at Urbana-Champaign)

  • Jiadiao Zhou

    (University of Illinois at Urbana-Champaign)

  • Yueji Wang

    (University of Illinois at Urbana-Champaign
    University of Illinois Urbana-Champaign)

  • Erik Russell Nelson

    (Cancer Center at Illinois (CCIL)
    University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-)

  • Qian Chen

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

  • Xiaojia Shelly Zhang

    (University of Illinois Urbana-Champaign
    University of Illinois at Urbana-Champaign
    National Center for Supercomputing Applications)

  • Wael Hassaneen

    (University of Illinois at Urbana-Champaign
    Carle Foundation Hospital)

  • Hua Wang

    (University of Illinois at Urbana-Champaign
    Cancer Center at Illinois (CCIL)
    University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

Abstract

As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8+ T cell response. These lead to 80% tumor-free survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines.

Suggested Citation

  • Rimsha Bhatta & Joonsu Han & Yusheng Liu & Yang Bo & David Lee & Jiadiao Zhou & Yueji Wang & Erik Russell Nelson & Qian Chen & Xiaojia Shelly Zhang & Wael Hassaneen & Hua Wang, 2023. "Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43914-8
    DOI: 10.1038/s41467-023-43914-8
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    References listed on IDEAS

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    1. Daniel Torralba & Francesc Baixauli & Carolina Villarroya-Beltri & Irene Fernández-Delgado & Ana Latorre-Pellicer & Rebeca Acín-Pérez & Noa B Martín-Cófreces & Ángel Luis Jaso-Tamame & Salvador Iborra, 2018. "Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    2. Jennifer A. Prescher & Danielle H. Dube & Carolyn R. Bertozzi, 2004. "Chemical remodelling of cell surfaces in living animals," Nature, Nature, vol. 430(7002), pages 873-877, August.
    3. Hua Wang & Alexander J. Najibi & Miguel C. Sobral & Bo Ri Seo & Jun Yong Lee & David Wu & Aileen Weiwei Li & Catia S. Verbeke & David J. Mooney, 2020. "Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. Bingfeng Zuo & Han Qi & Zhen Lu & Lu Chen & Bo Sun & Rong Yang & Yang Zhang & Zhili Liu & Xianjun Gao & Abin You & Li Wu & Renwei Jing & Qibing Zhou & HaiFang Yin, 2020. "Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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    1. Yue Jiang & Min Zhao & Jia Miao & Wan Chen & Yuan Zhang & Minqian Miao & Li Yang & Qing Li & Qingqing Miao, 2024. "Acidity-activatable upconversion afterglow luminescence cocktail nanoparticles for ultrasensitive in vivo imaging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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