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T-win® 技术:免疫调节疫苗。

The T-win® technology: immune-modulating vaccines.

机构信息

Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, DK-2730, Herlev, Denmark.

Department of Immunology and Microbiology, University of Copenhagen, DK-2200, Copenhagen, Denmark.

出版信息

Semin Immunopathol. 2019 Jan;41(1):87-95. doi: 10.1007/s00281-018-0695-8. Epub 2018 Jul 2.

DOI:10.1007/s00281-018-0695-8
PMID:29968045
Abstract

The T-win® technology is an innovative investigational approach designed to activate the body's endogenous anti-regulatory T cells (anti-Tregs) to target regulatory as well as malignant cells. Anti-Tregs are naturally occurring T cells that can directly react against regulatory immune cells because they recognize proteins that these targets express, including indoleamine 2,3-dioxygenase (IDO), tryptophan 2,6-dioxygenase, arginase, and programmed death ligand 1 (PD-L1). The T-win® technology is characterized by therapeutic vaccination with long peptide epitopes derived from these antigens and therefore offers a novel way to target genetically stable cells with regular human leukocyte antigen expression in the tumor microenvironment. The T-win® technology thus also represents a novel way to attract pro-inflammatory cells to the tumor microenvironment where they can directly affect immune inhibitory pathways, potentially altering tolerance to tumor antigens. The modification of an immune regulatory environment into a pro-inflammatory milieu potentiates effective anti-tumor T cell responses. Many regulatory immune cells may be reverted into effector cells given the right stimulus. Because T-win® technology is based on the immune-modulatory function of the vaccines, the vaccines activate both CD4 and CD8 anti-Tregs. Of importance, in clinical trials, vaccinations against IDO or PD-L1 to potentiate anti-Tregs have so far proved to be safe, with minimal toxicity.

摘要

T-win®技术是一种创新的研究方法,旨在激活机体内源性的抗调节性 T 细胞(anti-Tregs),以靶向调节性细胞和恶性细胞。Anti-Tregs 是天然存在的 T 细胞,因为它们可以识别这些靶标表达的蛋白质,包括吲哚胺 2,3-双加氧酶(IDO)、色氨酸 2,6-双加氧酶、精氨酸酶和程序性死亡配体 1(PD-L1),所以可以直接针对调节性免疫细胞。T-win®技术的特点是采用这些抗原的长肽表位进行治疗性疫苗接种,因此为靶向肿瘤微环境中具有常规人类白细胞抗原表达的遗传稳定细胞提供了一种新方法。因此,T-win®技术也代表了一种吸引促炎细胞进入肿瘤微环境的新方法,在肿瘤微环境中,它们可以直接影响免疫抑制途径,可能改变对肿瘤抗原的耐受性。将免疫调节环境修饰为促炎环境可以增强有效的抗肿瘤 T 细胞反应。在适当的刺激下,许多调节性免疫细胞可能被逆转成效应细胞。由于 T-win®技术基于疫苗的免疫调节功能,疫苗可以激活 CD4 和 CD8 anti-Tregs。重要的是,在临床试验中,针对 IDO 或 PD-L1 的疫苗接种以增强 anti-Tregs 迄今为止已被证明是安全的,毒性最小。

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本文引用的文献

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IDO takes a blow.吲哚胺2,3-双加氧酶受到冲击。
Nat Rev Drug Discov. 2018 Apr 27;17(5):307. doi: 10.1038/nrd.2018.67.
2
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.TGFβ 通过促使 T 细胞排除而减弱肿瘤对 PD-L1 阻断的反应。
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The Balance Players of the Adaptive Immune System.适应性免疫系统的平衡者。
Int J Mol Sci. 2024 Aug 15;25(16):8899. doi: 10.3390/ijms25168899.
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Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens.治疗性癌症疫苗与肿瘤微环境之间的双向串扰:超越肿瘤抗原
Fundam Res. 2022 Mar 26;3(6):1005-1024. doi: 10.1016/j.fmre.2022.03.009. eCollection 2023 Nov.
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TGFβ-specific T cells induced by a TGFβ-derived immune modulatory vaccine both directly and indirectly modulate the phenotype of tumor-associated macrophages and fibroblasts.由 TGFβ 衍生的免疫调节疫苗诱导的 TGFβ 特异性 T 细胞可直接和间接调节肿瘤相关巨噬细胞和成纤维细胞的表型。
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Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy.吲哚胺2,3-双加氧酶(IDO)活性:肿瘤免疫治疗实验室检测中的一种潜在生物标志物
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J Immunother Cancer. 2022 Dec;10(12). doi: 10.1136/jitc-2022-005491.
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Plasma and Urine Indoleamine 2,3-Dioxygenase Activity: Promising Biomarkers for Chronic Kidney Disease and Inflammation Status.血浆和尿液吲哚胺2,3-双加氧酶活性:慢性肾脏病和炎症状态的潜在生物标志物。
J Inflamm Res. 2022 Sep 7;15:5129-5139. doi: 10.2147/JIR.S378594. eCollection 2022.
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A New Generation of Vaccines in the Age of Immunotherapy.免疫治疗时代的新一代疫苗。
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Anti-regulatory T cells.抑制性 T 细胞。
Semin Immunopathol. 2017 Apr;39(3):317-326. doi: 10.1007/s00281-016-0593-x. Epub 2016 Sep 27.