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Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors

Author

Listed:
  • Hua Wang

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Alexander J. Najibi

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Miguel C. Sobral

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Bo Ri Seo

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Jun Yong Lee

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering
    The Catholic University of Korea)

  • David Wu

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Aileen Weiwei Li

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • Catia S. Verbeke

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

  • David J. Mooney

    (Harvard University
    Wyss Institute for Biologically Inspired Engineering)

Abstract

Poorly immunogenic tumors, including triple negative breast cancers (TNBCs), remain resistant to current immunotherapies, due in part to the difficulty of reprogramming the highly immunosuppressive tumor microenvironment (TME). Here we show that peritumorally injected, macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) for concentrating dendritic cells (DCs), CpG oligonucleotides, and a doxorubicin-iRGD conjugate enhance the immunogenic death of tumor cells, increase systemic tumor-specific CD8 + T cells, repolarize tumor-associated macrophages towards an inflammatory M1-like phenotype, and significantly improve antitumor efficacy against poorly immunogenic TNBCs. This system also prevents tumor recurrence after surgical resection and results in 100% metastasis-free survival upon re-challenge. This chemo-immunotherapy that concentrates DCs to present endogenous tumor antigens generated in situ may broadly serve as a facile platform to modulate the suppressive TME, and enable in situ personalized cancer vaccination.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19540-z
    DOI: 10.1038/s41467-020-19540-z
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    Cited by:

    1. Chaoyu Wang & Ruoshi Zhang & Jia He & Lvshan Yu & Xinyan Li & Junxia Zhang & Sai Li & Conggang Zhang & Jonathan C. Kagan & Jeffrey M. Karp & Rui Kuai, 2023. "Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Kaiyuan Wang & Yang Li & Xia Wang & Zhijun Zhang & Liping Cao & Xiaoyuan Fan & Bin Wan & Fengxiang Liu & Xuanbo Zhang & Zhonggui He & Yingtang Zhou & Dong Wang & Jin Sun & Xiaoyuan Chen, 2023. "Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. 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.

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