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Regulatory T cell-targeted hybrid nanoparticles combined with immuno-checkpoint blockage for cancer immunotherapy

Title
Regulatory T cell-targeted hybrid nanoparticles combined with immuno-checkpoint blockage for cancer immunotherapy
Author
최한곤
Keywords
Cancer immunotherapy; CTLA-4; Hybrid nanoparticles; Imatinib; tLyp1 peptide; Treg cell; DRUG-DELIVERY; METASTATIC MELANOMA; CARBON NANOTUBES; FOXP3 EXPRESSION; PARTICLE-SIZE; IN-VIVO; TUMOR; IMATINIB; RESPONSES; NEUROPILIN-1
Issue Date
2018-05
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v. 281, Page. 84-96
Abstract
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.
URI
https://www.sciencedirect.com/science/article/pii/S0168365918302839http://repository.hanyang.ac.kr/handle/20.500.11754/81194
ISSN
1873-4995; 0168-3659
DOI
10.1016/j.jconrel.2018.05.018
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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