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基于 HER2 的重组免疫原通过 FcγR 靶向 DC 用于癌症免疫治疗。

HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy.

机构信息

Department of Experimental Medicine, "Sapienza" University of Rome, Italy.

出版信息

J Mol Med (Berl). 2011 Dec;89(12):1231-40. doi: 10.1007/s00109-011-0794-7. Epub 2011 Aug 16.

DOI:10.1007/s00109-011-0794-7
PMID:21845448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3218291/
Abstract

Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364-391) and the Fc domain of a human IgG(1). In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8(+) T cells from breast cancer patients.

摘要

树突状细胞（DC）为基础的免疫疗法是一种很有吸引力的方法，旨在诱导持久的抗肿瘤效应细胞，以控制癌症的进展。在设计树突状细胞疫苗时，针对 DC 是一个关键步骤，目的是优化抗原的传递和加工，为此已经鉴定了几种受体。在这项研究中，我们在体外和体内都利用 FcγR 来靶向 DC。我们设计了一种重组分子（HER2-Fc），由人肿瘤相关抗原 HER2 的免疫原性序列（aa364-391）和人 IgG1 的 Fc 结构域组成。在小鼠模型中，HER2-Fc cDNA 疫苗接种可激活针对 HER2 肽表位的显著 T 细胞介导的免疫反应，如 IFN-γ ELIspot 检测所示，并诱导与 Ctrl-Fc 疫苗接种的对照小鼠相比更长的肿瘤潜伏期。人体外研究表明，重组 HER2-Fc 免疫原通过 FcγR 有效靶向人树突状细胞，导致蛋白质交叉加工，并激活来自乳腺癌患者的自体 HER2 特异性 CD8+T 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/e7516050d3c2/109_2011_794_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/aea970d60c2c/109_2011_794_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/29616d9815f6/109_2011_794_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/863e04b51a69/109_2011_794_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/9a9f8a0bc983/109_2011_794_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/e7516050d3c2/109_2011_794_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/aea970d60c2c/109_2011_794_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/29616d9815f6/109_2011_794_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/863e04b51a69/109_2011_794_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/9a9f8a0bc983/109_2011_794_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883f/3218291/e7516050d3c2/109_2011_794_Fig5_HTML.jpg

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本文引用的文献

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The first dendritic cell-based therapeutic cancer vaccine is approved by the FDA.首款基于树突状细胞的治疗性癌症疫苗获美国食品药品监督管理局批准。
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