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脂质体包裹的口服治疗性肽疫苗可减少结直肠癌原位小鼠模型中的肿瘤生长。

Lipid-encapsulated oral therapeutic peptide vaccines reduce tumour growth in an orthotopic mouse model of colorectal cancer.

机构信息

School of Pharmacy, University of Otago, Dunedin 9016, New Zealand.

Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.

出版信息

Eur J Pharm Biopharm. 2020 Jul;152:183-192. doi: 10.1016/j.ejpb.2020.04.020. Epub 2020 May 4.

Abstract

The aim of this study was to develop an oral vaccine that could be used to treat colorectal cancer. Oral vaccines are technically challenging to develop due to the harsh gastric environment but have numerous benefits including high patient acceptability and the potential to stimulate local mucosal immune responses. Therapeutic vaccines are being investigated as options to treat cancer and the generation of local mucosal immunity may be of benefit in the treatment of gastrointestinal cancers. Novel oral vaccines consisting of a long tumour peptide and the TLR2 (Toll-like receptor 2) ligand PamCys, formulated in either liposomes or W/O/W double emulsions, were developed. Oral dosing with the emulsion vaccine increased the numbers of activated T cells, B cells and CD11cF4/80CD11b cells compared to mice that received control vaccines. In an orthotopic mouse model of colorectal cancer these immunological changes were associated with a seven-fold reduction in tumour size.

摘要

这项研究的目的是开发一种可用于治疗结直肠癌的口服疫苗。由于胃部环境恶劣,口服疫苗的开发具有技术挑战性,但具有许多益处,包括患者高度接受和刺激局部黏膜免疫反应的潜力。治疗性疫苗正在被研究作为治疗癌症的选择,局部黏膜免疫可能对胃肠道癌症的治疗有益。开发了由长肿瘤肽和 TLR2(Toll 样受体 2)配体 PamCys 组成的新型口服疫苗,分别以脂质体或 W/O/W 双重乳液的形式配制。与接受对照疫苗的小鼠相比,用乳剂疫苗口服给药增加了活化的 T 细胞、B 细胞和 CD11cF4/80CD11b 细胞的数量。在结直肠原位癌小鼠模型中,这些免疫变化与肿瘤大小减少七倍相关。

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