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Toll-like receptor 3-induced immune response by poly(D,L-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy

Authors Han HD, Byeon YS, Kang TH, Jung ID, Lee JW, Shin BC, Lee YJ, Sood AK, Park YM

Received 22 March 2016

Accepted for publication 24 September 2016

Published 2 November 2016 Volume 2016:11 Pages 5729—5742


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster

Hee Dong Han,1,* Yeongseon Byeon,1,* Tae Heung Kang,1 In Duk Jung,1 Jeong-Won Lee,2 Byung Cheol Shin,3 Young Joo Lee,4 Anil K Sood,5–7 Yeong-Min Park1

1Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do, 2Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 3Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, 4Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, South Korea; 5Department of Gynecologic Oncology and Reproductive Medicine, 6Department of Cancer Biology, 7Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, TX, USA

*These authors contributed equally to this work

Abstract: Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(D,L-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation. The PLGA-NPs were taken up by DCs, and their uptake greatly facilitated major histocompatibility class I antigen presentation in vitro. Moreover, vaccination with PLGA-NP-treated DCs led to the generation of ovalbumin-specific CD8+ T cells, and the resulting antitumor efficacy was significantly increased in EG.7 and TC-1 tumor-bearing mice compared to control mice (P<0.01). Taken together, these findings demonstrated that the PLGA-NP platform may be an effective method for delivering tumor-specific antigens or adjuvants to DCs.

Keywords: cancer immunotherapy, PLGA nanoparticles, antigen delivery

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