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Sci Adv. 2020 Mar 25;6(13):eaay1601. doi: 10.1126/sciadv.aay1601. eCollection 2020 Mar.

Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer.

Author information

1
Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
2
Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA.
3
National Taiwan University, Taipei 10617, Taiwan.
4
Department of Oncology, Sidney Kimmel Comprehensive Cancer Centre, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
5
micromod Partikeltechnologie GmbH, Rostock, Germany.
6
Department of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Centre, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
7
Department of Urology, James Buchanan Brady Urological Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
8
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA.
9
Institute for NanoBioTechnology, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA.

Abstract

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand ("active targeting") is superior to its unlabeled counterpart ("passive targeting"). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8+ T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.

PMID:
32232146
PMCID:
PMC7096167
DOI:
10.1126/sciadv.aay1601

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