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基于工程 Grp170 的免疫调节剂用于癌症免疫治疗。

Engineering Grp170-based immune modulators for cancer immunotherapy.

机构信息

Department of Human and Molecular Genetics; Virginia Commonwealth University School of Medicine; Richmond, VA USA ; VCU Institute of Molecular Medicine; Virginia Commonwealth University School of Medicine; Richmond, VA USA ; VCU Massey Cancer Center; Virginia Commonwealth University School of Medicine; Richmond, VA USA.

出版信息

Oncoimmunology. 2013 Jun 1;2(6):e24385. doi: 10.4161/onci.24385. Epub 2013 May 14.

DOI:10.4161/onci.24385
PMID:23894699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3716734/
Abstract

We have recently demonstrated that glucose-regulated protein 170 (Grp170), a stress-responsive molecular chaperone of the endoplasmic reticulum, can be exploited to stimulate anticancer immunity due to its superior antigen chaperoning and delivering capacity. The immune remodeling of the tumor microenvironment induced by a Grp170-based chaperone leads to immune responses that effectively control the progression of both primary neoplasms and their metastases. Our findings support the development of Grp170-based immunomodulating strategies to potentiate antitumor immune responses.

摘要

我们最近的研究表明，葡萄糖调节蛋白 170（Grp170）是内质网应激反应的分子伴侣，由于其卓越的抗原伴侣和递呈能力，可被用于刺激抗癌免疫。基于 Grp170 的分子伴侣重塑肿瘤微环境，引发免疫反应，有效控制原发性肿瘤及其转移灶的进展。我们的研究结果支持开发基于 Grp170 的免疫调节策略，以增强抗肿瘤免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70a/3716734/acc84b77f1c9/onci-2-e24385-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70a/3716734/acc84b77f1c9/onci-2-e24385-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70a/3716734/acc84b77f1c9/onci-2-e24385-g1.jpg

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Engineering Grp170-based immune modulators for cancer immunotherapy.基于工程 Grp170 的免疫调节剂用于癌症免疫治疗。
Oncoimmunology. 2013 Jun 1;2(6):e24385. doi: 10.4161/onci.24385. Epub 2013 May 14.
2
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本文引用的文献

1
A multifunctional chimeric chaperone serves as a novel immune modulator inducing therapeutic antitumor immunity.多功能嵌合分子伴侣作为一种新型免疫调节剂，诱导治疗性抗肿瘤免疫。
Cancer Res. 2013 Apr 1;73(7):2093-103. doi: 10.1158/0008-5472.CAN-12-1740. Epub 2013 Jan 18.
2
Superior antitumor response induced by large stress protein chaperoned protein antigen compared with peptide antigen.大应激蛋白伴侣蛋白抗原诱导的抗肿瘤反应优于肽抗原。
J Immunol. 2010 Jun 1;184(11):6309-19. doi: 10.4049/jimmunol.0903891. Epub 2010 May 3.
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Secretable chaperone Grp170 enhances therapeutic activity of a novel tumor suppressor, mda-7/IL-24.
一种含有神经突肽和grp170的新型纳米颗粒可诱导细胞毒性T淋巴细胞反应以抑制肿瘤生长。
J Neurooncol. 2015 Oct;125(1):23-32. doi: 10.1007/s11060-015-1884-0. Epub 2015 Aug 20.
可分泌伴侣蛋白Grp170增强新型肿瘤抑制因子mda-7/IL-24的治疗活性。
Cancer Res. 2008 May 15;68(10):3890-8. doi: 10.1158/0008-5472.CAN-08-0156.
4
Activation of NF-kappaB by the intracellular expression of NF-kappaB-inducing kinase acts as a powerful vaccine adjuvant.通过核因子κB诱导激酶的细胞内表达激活核因子κB可作为一种强效疫苗佐剂。
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14459-64. doi: 10.1073/pnas.0603493103. Epub 2006 Sep 13.
5
Extracellular targeting of endoplasmic reticulum chaperone glucose-regulated protein 170 enhances tumor immunity to a poorly immunogenic melanoma.内质网伴侣葡萄糖调节蛋白170的细胞外靶向增强了对低免疫原性黑色素瘤的肿瘤免疫。
J Immunol. 2006 Aug 1;177(3):1543-51. doi: 10.4049/jimmunol.177.3.1543.
6
Molecular chaperones and cancer immunotherapy.分子伴侣与癌症免疫疗法。
Handb Exp Pharmacol. 2006(172):305-29. doi: 10.1007/3-540-29717-0_13.
7
Toll-dependent selection of microbial antigens for presentation by dendritic cells.树突状细胞通过Toll依赖性方式选择微生物抗原进行呈递。
Nature. 2006 Apr 6;440(7085):808-12. doi: 10.1038/nature04596. Epub 2006 Feb 19.
8
Chaperoning function of stress protein grp170, a member of the hsp70 superfamily, is responsible for its immunoadjuvant activity.应激蛋白grp170是热休克蛋白70超家族的成员之一，其陪伴功能决定了它的免疫佐剂活性。
Cancer Res. 2006 Jan 15;66(2):1161-8. doi: 10.1158/0008-5472.CAN-05-2609.
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Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity.热休克蛋白110和葡萄糖调节蛋白170作为癌症疫苗的特性以及发热范围热疗对疫苗活性的影响。
J Immunol. 2001 Jan 1;166(1):490-7. doi: 10.4049/jimmunol.166.1.490.
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The hsp110 and Grp1 70 stress proteins: newly recognized relatives of the Hsp70s.热休克蛋白110和葡萄糖调节蛋白70应激蛋白：热休克蛋白70家族新发现的亲属
Cell Stress Chaperones. 2000 Oct;5(4):276-90. doi: 10.1379/1466-1268(2000)005<0276:thagsp>2.0.co;2.