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

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 Xie, Thomas C. Havighurst, Ishan Chakravarty, Alexander L. Rakhmilevich, Kathleen A. O’Leary, Linda A. Schuler, Paul M. Sondel, Kyungmann Kim, Shaoqin Gong () and Zachary S. Morris ()
Additional contact information
Ying Zhang: 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
Wonjong Jin: University of Wisconsin-Madison
Yuyuan Wang: University of Wisconsin-Madison
Amber Bates: University of Wisconsin-Madison
Caroline P. Kerr: University of Wisconsin-Madison
Trang Le: University of Wisconsin-Madison
Raad Allawi: University of Wisconsin-Madison
Xiuxiu Wang: University of Wisconsin-Madison
Ruosen Xie: 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
Kyungmann Kim: University of Wisconsin-Madison
Shaoqin Gong: University of Wisconsin-Madison
Zachary S. Morris: University of Wisconsin-Madison

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32645-x

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