Peptide-mediated targeting of cytokines to tumor vasculature: the NGR-hTNF example.
Peptide-mediated targeting of cytokines to tumor vasculature: the NGR-hTNF example.
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DOI：
10.1007/s40259-013-0048-z
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Gregorc V
中科院分区：
文献类型：
--
作者：
Corti A;Curnis F;Rossoni G;Marcucci F;Gregorc V
越来越多的证据表明，细胞因子在癌症治疗中的功效可以通过基于与识别由肿瘤细胞或肿瘤微环境的元素（包括肿瘤脉管系统）表达的受体的配体缀合的靶向策略来增加。靶向方法通常被认为允许给予低剂量但无活性的药物，从而避免毒性反应。然而，越来越清楚的是，在细胞因子的情况下，这种策略具有另一个固有的优点，即施用极低剂量的可能性，其不激活系统性反调节机制，这可能限制其潜在的治疗效果。本文综述了肿瘤血管归巢肽作为细胞因子靶向输送到肿瘤血管的载体。特别是，我们提供了用含有NGR、RGD、isoDGR或RGR序列的肽制备的肽-细胞因子缀合物的概述，并更详细地描述了NGR-hTNF的生物学和药理学性质，NGR-hTNF是一种肽-肿瘤坏死因子-α缀合物，目前正在II期和III期临床研究中进行测试。用这些产品进行的临床前和临床研究的结果表明，肽介导的血管靶向确实是将生物活性量的细胞因子递送至肿瘤内皮细胞而不引起反调节机制的激活和毒性反应的可行策略。
A growing body of evidence suggests that the efficacy of cytokines in cancer therapy can be increased by targeting strategies based on conjugation with ligands that recognize receptors expressed by tumor cells or elements of the tumor microenvironment, including the tumor vasculature. The targeting approach is generally conceived to permit administration of low, yet pharmacologically active, doses of drugs, thereby avoiding toxic reactions. However, it is becoming clear that, in the case of cytokines, this strategy has another inherent advantage, i.e. the possibility of administering extremely low doses that do not activate systemic counter-regulatory mechanisms, which may limit their potential therapeutic effects. This review is focused on the use of tumor vasculature-homing peptides as vehicles for targeted delivery of cytokines to tumor blood vessel. In particular, we provide an overview of peptide-cytokine conjugates made with peptides containing the NGR, RGD, isoDGR or RGR sequences and describe, in more details, the biological and pharmacological properties of NGR-hTNF, a peptide-tumor necrosis factor-α conjugate that is currently being tested in phase II and III clinical studies. The results of preclinical and clinical studies performed with these products suggest that peptide-mediated vascular-targeting is indeed a viable strategy for delivering bioactive amounts of cytokines to tumor endothelial cells without causing the activation of counter-regulatory mechanisms and toxic reactions.
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影响因子：
11.5
作者：
Balza, E;Mortara, L;Borsi, L
通讯作者：
Borsi, L
影响因子：
20.3
作者：
Bieker, Ralf;Kessler, Torsten;Berdel, Wolfgang E.
通讯作者：
Berdel, Wolfgang E.
影响因子：
11.2
作者：
Curnis, F;Gasparri, A;Corti, A
通讯作者：
Corti, A
影响因子：
4
作者：
Corti, Angelo;Curnis, Flavio
通讯作者：
Curnis, Flavio
DOI：
10.1161/01.atv.0000245807.65714.0b
发表时间：
2006-12-01
影响因子：
8.7
作者：
Buehler, Alexandra;van Zandvoort, Marc A. M. J.;de Muinck, Ebo D.
通讯作者：
de Muinck, Ebo D.