Journal
JOURNAL OF CONTROLLED RELEASE
Volume 281, Issue -, Pages 84-96Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.05.018
Keywords
Cancer immunotherapy; CTLA-4; Hybrid nanoparticles; Imatinib; tLyp1 peptide; Treg cell
Funding
- National Research Foundation of Korea (NRF) grant - Korea Government (MSIP) [2015R1A2A2A01004118, 2015R1A2A2A04004806]
- Medical Research Center Program through the NRF grant [2015R1A5A2009124]
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Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation. In addition, an in vivo study revealed high tumor accumulation of the hybrid nanoparticle. Specifically, prolonged survival rate, enhanced tumor inhibition, reduced intratumoral Treg cells, and elevated intratumoral CD8(+) T cells against tumor were observed when combined with checkpoint-blockade by using anti-cytotoxic T-lymphocyte antigen-4 antibody. This study provided groundwork for a repertoire of nanoparticle-based drugs for targeting and modulating Treg cell function in the tumor microenvironment and for improving antitumor immunotherapy.
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