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

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 tu...

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Bibliographic Details
Published in:Journal of controlled release 2018-07, Vol.281, p.84-96
Main Authors: Ou, Wenquan, Thapa, Raj Kumar, Jiang, Liyuan, Soe, Zar Chi, Gautam, Milan, Chang, Jae-Hoon, Jeong, Jee-Heon, Ku, Sae Kwang, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cancer immunotherapy
CD8-Positive T-Lymphocytes - drug effects
Cell Line, Tumor
Cell Survival - drug effects
CTLA-4
CTLA-4 Antigen - metabolism
Humans
Hybrid nanoparticles
Imatinib
Imatinib Mesylate - pharmacology
Immunosuppression - methods
Immunotherapy - methods
Mice, Inbred C57BL
Nanoparticles - metabolism
Neoplasms - drug therapy
Neoplasms - immunology
Neoplasms - pathology
Neoplasms - therapy
Peptides - chemistry
Phosphorylation
STAT3 Transcription Factor - metabolism
STAT5 Transcription Factor - metabolism
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Regulatory - metabolism
tLyp1 peptide
Treg cell
Tumor Microenvironment
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Summary: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. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2018.05.018