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Multifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade

Author

Listed:
  • Ying Zhang

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Raghava N. Sriramaneni

    (University of Wisconsin-Madison)

  • Paul A. Clark

    (University of Wisconsin-Madison)

  • Justin C. Jagodinsky

    (University of Wisconsin-Madison)

  • Mingzhou Ye

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Wonjong Jin

    (University of Wisconsin-Madison)

  • Yuyuan Wang

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Amber Bates

    (University of Wisconsin-Madison)

  • Caroline P. Kerr

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Trang Le

    (University of Wisconsin-Madison)

  • Raad Allawi

    (University of Wisconsin-Madison)

  • Xiuxiu Wang

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Ruosen Xie

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Thomas C. Havighurst

    (University of Wisconsin-Madison)

  • Ishan Chakravarty

    (University of Wisconsin-Madison)

  • Alexander L. Rakhmilevich

    (University of Wisconsin-Madison)

  • Kathleen A. O’Leary

    (University of Wisconsin-Madison)

  • Linda A. Schuler

    (University of Wisconsin-Madison)

  • Paul M. Sondel

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Kyungmann Kim

    (University of Wisconsin-Madison)

  • Shaoqin Gong

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Zachary S. Morris

    (University of Wisconsin-Madison)

Abstract

Radiation therapy (RT) activates an in situ vaccine effect when combined with immune checkpoint blockade (ICB), yet this effect may be limited because RT does not fully optimize tumor antigen presentation or fully overcome suppressive mechanisms in the tumor-immune microenvironment. To overcome this, we develop a multifunctional nanoparticle composed of polylysine, iron oxide, and CpG (PIC) to increase tumor antigen presentation, increase the ratio of M1:M2 tumor-associated macrophages, and enhance stimulation of a type I interferon response in conjunction with RT. In syngeneic immunologically “cold” murine tumor models, the combination of RT, PIC, and ICB significantly improves tumor response and overall survival resulting in cure of many mice and consistent activation of tumor-specific immune memory. Combining RT with PIC to elicit a robust in situ vaccine effect presents a simple and readily translatable strategy to potentiate adaptive anti-tumor immunity and augment response to ICB or potentially other immunotherapies.

Suggested Citation

  • Ying Zhang & Raghava N. Sriramaneni & Paul A. Clark & Justin C. Jagodinsky & Mingzhou Ye & Wonjong Jin & Yuyuan Wang & Amber Bates & Caroline P. Kerr & Trang Le & Raad Allawi & Xiuxiu Wang & Ruosen Xi, 2022. "Multifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32645-x
    DOI: 10.1038/s41467-022-32645-x
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    1. Christina Twyman-Saint Victor & Andrew J. Rech & Amit Maity & Ramesh Rengan & Kristen E. Pauken & Erietta Stelekati & Joseph L. Benci & Bihui Xu & Hannah Dada & Pamela M. Odorizzi & Ramin S. Herati & , 2015. "Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer," Nature, Nature, vol. 520(7547), pages 373-377, April.
    2. Sidi A. Bencherif & R. Warren Sands & Omar A. Ali & Weiwei A. Li & Sarah A. Lewin & Thomas M. Braschler & Ting-Yu Shih & Catia S. Verbeke & Deen Bhatta & Glenn Dranoff & David J. Mooney, 2015. "Injectable cryogel-based whole-cell cancer vaccines," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    3. Claire Vanpouille-Box & Amandine Alard & Molykutty J. Aryankalayil & Yasmeen Sarfraz & Julie M. Diamond & Robert J. Schneider & Giorgio Inghirami & C. Norman Coleman & Silvia C. Formenti & Sandra Dema, 2017. "DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
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    Cited by:

    1. Dongkyu Kang & Hyung Shik Kim & Soohyun Han & Yeonju Lee & Young-Pil Kim & Dong Yun Lee & Joonseok Lee, 2023. "A local water molecular-heating strategy for near-infrared long-lifetime imaging-guided photothermal therapy of glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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