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展示 GP2 肽的 Lambda 噬菌体纳米颗粒在小鼠 TUBO 肿瘤模型中诱导预防性和治疗性活性。

Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice.

机构信息

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

School of Pharmacy, University of Waterloo, Waterloo, Canada.

出版信息

Sci Rep. 2019 Feb 18;9(1):2221. doi: 10.1038/s41598-018-38371-z.

Abstract

Generating a protective and long-lasting immune response is the primary goal in the expanding field of immunotherapeutic research. In current study we designed an immunogenic bacteriophage- based vaccine to induce a cytotoxic T lymphocyte activity against a mice tumor model over-expressing HER2/neu. Bacteriophage λ displaying a HER2/neu derived peptide GP2 was constructed and used as an anti-cancer vaccine in a BALB/c mouse xenograft tumor model. The results of our study indicated that phage nanoparticles displaying GP2 as a fused peptide to the gpD phage capsid protein induced a robust CTL response. Furthermore, the chimeric phage nanoparticles protected mice against HER2/neu-positive tumor challenge in both prophylactic and therapeutic settings. In conclusion, we propose that λ phage nanoparticles decorated with GP2 peptide merit further investigation for the development of peptide-based vaccines against HER2/neu overexpressing tumors.

摘要

产生保护性和持久的免疫反应是免疫治疗研究领域不断扩大的主要目标。在本研究中,我们设计了一种免疫原性噬菌体疫苗,以诱导过表达 HER2/neu 的小鼠肿瘤模型中的细胞毒性 T 淋巴细胞活性。构建了展示 HER2/neu 衍生肽 GP2 的噬菌体 λ,并将其用作 BALB/c 小鼠异种移植肿瘤模型中的抗癌疫苗。我们的研究结果表明,展示与 gpD 噬菌体衣壳蛋白融合的 GP2 肽的噬菌体纳米颗粒诱导了强烈的 CTL 反应。此外,嵌合噬菌体纳米颗粒在预防性和治疗性设置中均能保护小鼠免受 HER2/neu 阳性肿瘤的挑战。总之,我们提出用 GP2 肽装饰的 λ 噬菌体纳米颗粒值得进一步研究,以开发针对过表达 HER2/neu 的肿瘤的基于肽的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0655/6379380/ece1e20dbd79/41598_2018_38371_Fig1_HTML.jpg

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