Journal
ADVANCED MATERIALS
Volume 31, Issue 43, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201902626
Keywords
cancer immunotherapy; nanoparticles; radiation; vaccines
Categories
Funding
- National Institute of Health [1DP5OD024576-01, U01CA233102, R01HL129785]
- University of Wisconsin Carbone Cancer Center Support Grant [P30 CA014520]
- Bentson Translational Research Fellowship
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Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized by T cells. Among immunologically cold tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These cold tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of cold tumors, resulting in a more diversified antitumor T-cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane-coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T-cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor-specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off-the-shelf therapeutics.
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