Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Yuanzeng Min; Kyle C Roche; Shaomin Tian; Michael J Eblan; Karen P McKinnon; Joseph M Caster; Shengjie Chai; Laura E Herring; Longzhen Zhang; Tian Zhang; Joseph M DeSimone; Joel E Tepper; Benjamin G Vincent; Jonathan S Serody; Andrew Z Wang

doi:10.1038/nnano.2017.113

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Nat Nanotechnol. 2017 Sep;12(9):877-882. doi: 10.1038/nnano.2017.113. Epub 2017 Jun 26.

Authors

Yuanzeng Min^{1

2

3}, Kyle C Roche^{1

2

3}, Shaomin Tian^{2

4}, Michael J Eblan^{1

2

3}, Karen P McKinnon^{2

4}, Joseph M Caster^{1

2

3}, Shengjie Chai^{2

5}, Laura E Herring⁶, Longzhen Zhang⁷, Tian Zhang⁸, Joseph M DeSimone^{2

4

9

10

11

12}, Joel E Tepper^{1

2

3}, Benjamin G Vincent^{2

5}, Jonathan S Serody^{2

4

5}, Andrew Z Wang^{1

2

3

7}

Affiliations

¹ Laboratory of Nano- and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
³ Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
⁴ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
⁵ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
⁶ UNC Proteomics Core Facility, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
⁷ Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
⁸ Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
⁹ Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
¹⁰ Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
¹¹ Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, USA.
¹² Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. 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 αPD-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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / immunology*
CD4-CD8 Ratio
Cell Line, Tumor
Female
Immunotherapy / methods*
Melanoma, Experimental / immunology
Melanoma, Experimental / therapy*
Mice, Inbred C57BL
Nanomedicine / methods
Nanoparticles / therapeutic use*
Neoplasms / immunology
Neoplasms / therapy
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
T-Lymphocytes, Cytotoxic / immunology

Substances

Antigens, Neoplasm
Programmed Cell Death 1 Receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding