한빛사논문
- 조회1,808
Abstract
Sun-Young Kim1, Hathaichanok Phuengkham1, Young-Woock Noh1, Hong-Guen Lee2, Soong Ho Um2 and Yong Taik Lim1,2,*
1SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Jangan-gu, Suwon, Gyeonggi-do, Republic of Korea
2School of Chemical Engineering, Sungkyunkwan University, Jangan-gu, Suwon, Gyeonggi-do, Republic of Korea
*Corresponding author
Abstract
The well-designed activation of dendritic cells (DCs) by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen-antibody immune complexes (ICs) are known to directly bind to and cross-link Fc-gamma receptors (FcγRs) on DCs, which induce enhanced migration of DCs to draining lymph nodes through the up-regulation of the chemokine receptor CCR7 and cross-presentation inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. In this study, ICs mimicking synthetic vaccine nanoparticles (NPs) are designed and synthesized by the coating of poly (lactic-co-glycolic acid) (PLGA) NPs containing adjuvant (CpG oligodeoxynuleotides (ODNs) as toll-like receptor 9 ligands) with ovalbumin (OVA) proteins (as model antigens) and by the formation of OVA–OVA antibody ICs. Through the combination of FcγRs-mediated efficient antigen uptake and CpG ODNs-based immunostimulation, the secretion of TNF-α (12.3-fold), IL-6 (7.29-fold), and IL-12 (11-fold), homing ability to lymph nodes (7.5-fold), and cross-presentation (83.8-fold IL-2 secretion) are dramatically increased in DCs treated with PLGA(IC/CpG) NPs. Furthermore, mice vaccinated with DCs treated with PLGA(IC/CpG) NPs induced significant tumor (EG7-OVA) growth inhibition as well as prolonged survival through CTL-mediated enhanced cytotoxicity, antigen-specific responses, and IFN-γ secretion.
Keywords:
cancer immunotherapy;dendritic cells;immune complexes;lymph nodes;T cells
논문정보
- Research article
- 2016년 11월 (BRIC 등록일 2016-12-09)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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