4.8 Article

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

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NATURE NANOTECHNOLOGY
卷 12, 期 9, 页码 877-+

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NATURE PUBLISHING GROUP
DOI: 10.1038/NNANO.2017.113

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资金

  1. University of North Carolina (UNC) Flow Cytometry Core Facility [P30 CA016086]
  2. National Institutes of Health (NIH)/National Cancer Institute (NCI) [U54CA198999]
  3. Carolina Center of Cancer Nanotechnology Excellence (CCNE) Nano Approaches to Modulate Host Cell Response for Cancer Therapy)
  4. UNC University Cancer Research Fund
  5. Paul Calabresi Oncology K12 Award
  6. UNC CCNE Pilot Grant
  7. NIH/NCI [U54 CA151652, R01 CA178748, R21 CA182322]

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Immunotherapy holds tremendous promise for improving cancer treatment(1). To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'(2). Unfortunately, response rates for this strategy remain low(3). Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of alpha PD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4(+)T/T-reg and CD8(+)T/T-reg ratios (T-reg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

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