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一种新型的含 CpG 寡脱氧核苷酸的乳剂型佐剂增强了 CD8+T 细胞介导的抗肿瘤免疫。

A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8+ T-cell-mediated anti-tumor immunity.

机构信息

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.

出版信息

J Control Release. 2014 Jan 10;173:158-65. doi: 10.1016/j.jconrel.2013.10.027. Epub 2013 Oct 29.

Abstract

PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-ε-caprolactone) (PEG-b-PLACL), Span®85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b)-restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-γ-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy.

摘要

PELC 是一种新型乳剂型佐剂,包含可生物降解聚合物聚乙二醇-嵌段-聚(乳酸-共-ε-己内酯)(PEG-b-PLACL)、Span®85 和角鲨烯。为了研究 PELC 是否能够增强用于治疗肿瘤的抗原的 CTL 反应,将源自 HPV16 E7 的肽或蛋白抗原与 PELC 纳米颗粒和 CpG 寡脱氧核苷酸进行了配方。我们发现 PELC 配方可以体外和体内延迟抗原的释放。我们评估了与 PELC 或 PELC/CpG 配制的 H-2D(b)-限制性 CTL 表位 RAHYNIVTF(RAH)的免疫原性,并研究了这些配方促进肿瘤消退的能力。在小鼠单次皮下注射后,我们发现与 PELC 或 CpG 单独配制的 RAH 相比,与 PELC/CpG 配制的 RAH 肽(RAH/PELC/CpG)导致 IFN-γ 分泌细胞和 RAH 特异性 CD8(+)T 细胞数量增加,并且细胞毒性 T 细胞反应增强。荷瘤小鼠接受了 RAH/PELC/CpG 的单次注射,诱导了完全的肿瘤消退。这些结果表明,与 PELC/CpG 纳米颗粒配制的肽抗原可用于癌症免疫治疗。

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