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Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression

Author

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  • Jianqin Lu

    (Department of Medicine, David Geffen School of Medicine, University of California
    California NanoSystems Institute, University of California
    University of California)

  • Xiangsheng Liu

    (Department of Medicine, David Geffen School of Medicine, University of California
    University of California)

  • Yu-Pei Liao

    (Department of Medicine, David Geffen School of Medicine, University of California)

  • Felix Salazar

    (Department of Molecular and Medical Pharmacology Crump Institute for Molecular Imaging, David Geffen School of Medicine)

  • Bingbing Sun

    (Department of Medicine, David Geffen School of Medicine, University of California)

  • Wen Jiang

    (California NanoSystems Institute, University of California)

  • Chong Hyun Chang

    (California NanoSystems Institute, University of California
    University of California)

  • Jinhong Jiang

    (California NanoSystems Institute, University of California)

  • Xiang Wang

    (California NanoSystems Institute, University of California)

  • Anna M. Wu

    (Department of Molecular and Medical Pharmacology Crump Institute for Molecular Imaging, David Geffen School of Medicine)

  • Huan Meng

    (Department of Medicine, David Geffen School of Medicine, University of California
    California NanoSystems Institute, University of California
    University of California
    University of California)

  • Andre E. Nel

    (Department of Medicine, David Geffen School of Medicine, University of California
    California NanoSystems Institute, University of California
    University of California
    University of California)

Abstract

While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of the immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through the induction of immunogenic cell death (ICD) as well as interfering in the immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer that encapsulates mesoporous silica nanoparticles (MSNP). The porous MSNP interior allows contemporaneous delivery of the ICD-inducing chemotherapeutic agent, oxaliplatin (OX). The nanovesicles plus free OX or OX/IND-MSNP induce effective innate and adaptive anti-PDAC immunity when used in a vaccination approach, direct tumor injection or intravenous biodistribution to an orthotopic PDAC site. Significant tumor reduction or eradication is accomplishable by recruiting cytotoxic T lymphocytes, concomitant with downregulation of Foxp3+ T cells.

Suggested Citation

  • Jianqin Lu & Xiangsheng Liu & Yu-Pei Liao & Felix Salazar & Bingbing Sun & Wen Jiang & Chong Hyun Chang & Jinhong Jiang & Xiang Wang & Anna M. Wu & Huan Meng & Andre E. Nel, 2017. "Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01651-9
    DOI: 10.1038/s41467-017-01651-9
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    Cited by:

    1. Zhiren Wang & Wenpan Li & Yanhao Jiang & Jonghan Park & Karina Marie Gonzalez & Xiangmeng Wu & Qing-Yu Zhang & Jianqin Lu, 2024. "Cholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Huapan Fang & Zhaopei Guo & Jie Chen & Lin Lin & Yingying Hu & Yanhui Li & Huayu Tian & Xuesi Chen, 2021. "Combination of epigenetic regulation with gene therapy-mediated immune checkpoint blockade induces anti-tumour effects and immune response in vivo," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Jingchao Li & Yu Luo & Ziling Zeng & Dong Cui & Jiaguo Huang & Chenjie Xu & Liping Li & Kanyi Pu & Ruiping Zhang, 2022. "Precision cancer sono-immunotherapy using deep-tissue activatable semiconducting polymer immunomodulatory nanoparticles," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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