Exosome removal as a therapeutic adjuvant in cancer.
Exosome removal as a therapeutic adjuvant in cancer.
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DOI：
10.1186/1479-5876-10-134
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发表时间：
2012-06-27
影响因子：
7.4
通讯作者：
Tullis RH
中科院分区：
文献类型：
--
作者：
Marleau AM;Chen CS;Joyce JA;Tullis RH
由于这些纳米颗粒在肿瘤生长、免疫抑制、肿瘤血管生成和治疗耐药中的作用，外体分泌是恶性肿瘤的一个显著特征。Exosome是多种细胞在正常生理过程中释放的30-100 nm的膜泡。肿瘤异常地分泌大量外体，运输癌蛋白和免疫抑制分子来支持肿瘤的生长和转移。外切体在细胞间信号传递中的作用以人表皮生长因子受体2型(HER2)过表达的乳腺癌为例，在乳腺癌中，外切体与HER2癌蛋白一起刺激肿瘤生长，并干扰治疗性抗体Herceptin®的活性。由于来自实验模型系统的大量观察表明外切体在癌症中具有重要的临床影响，因此已经提出了几种针对其恶性活动的药理学策略。我们还提出了一种新的设备策略，涉及使用称为埃特隆Adapt™(适应性透析类亲和平台技术)系统的亲和血浆置换平台从整个循环系统体外血液滤过外体，该系统将克服药物方法带来的毒性和药物相互作用的风险。这项技术允许亲和剂，包括外切体结合凝集素和抗体，固定在整合到现有肾脏透析系统中的血浆滤膜的外部毛细血管空间中。从该平台发展而来的设备疗法允许快速体外捕获并选择性地从整个循环系统中保留目标粒子 <； 200 nm。这一策略得到了丙型肝炎病毒感染患者的临床经验的支持，该患者使用Adapt™设备血液净化器®，以减少与癌症外切体具有相似大小和糖化表面的病毒粒子的全身负荷。这篇综述讨论了针对癌症患者免疫抑制外切体的可能的治疗方法，以及这些策略对于逆转免疫功能障碍和改善对标准护理治疗的反应的预期意义。
Exosome secretion is a notable feature of malignancy owing to the roles of these nanoparticles in cancer growth, immune suppression, tumor angiogenesis and therapeutic resistance. Exosomes are 30–100 nm membrane vesicles released by many cells types during normal physiological processes. Tumors aberrantly secrete large quantities of exosomes that transport oncoproteins and immune suppressive molecules to support tumor growth and metastasis. The role of exosomes in intercellular signaling is exemplified by human epidermal growth factor receptor type 2 (HER2) over-expressing breast cancer, where exosomes with the HER2 oncoprotein stimulate tumor growth and interfere with the activity of the therapeutic antibody Herceptin®. Since numerous observations from experimental model systems point toward an important clinical impact of exosomes in cancer, several pharmacological strategies have been proposed for targeting their malignant activities. We also propose a novel device strategy involving extracorporeal hemofiltration of exosomes from the entire circulatory system using an affinity plasmapheresis platform known as the Aethlon ADAPT™ (adaptive dialysis-like affinity platform technology) system, which would overcome the risks of toxicity and drug interactions posed by pharmacological approaches. This technology allows affinity agents, including exosome-binding lectins and antibodies, to be immobilized in the outer-capillary space of plasma filtration membranes that integrate into existing kidney dialysis systems. Device therapies that evolve from this platform allow rapid extracorporeal capture and selective retention of target particles < 200 nm from the entire circulatory system. This strategy is supported by clinical experience in hepatitis C virus-infected patients using an ADAPT™ device, the Hemopurifier®, to reduce the systemic load of virions having similar sizes and glycosylated surfaces as cancer exosomes. This review discusses the possible therapeutic approaches for targeting immune suppressive exosomes in cancer patients, and the anticipated significance of these strategies for reversing immune dysfunction and improving responses to standard of care treatments.
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影响因子：
11.2
作者：
Ashiru O;Boutet P;Fernández-Messina L;Agüera-González S;Skepper JN;Valés-Gómez M;Reyburn HT
通讯作者：
Reyburn HT
影响因子：
4.4
作者：
Clayton, Aled;Al-Taei, Saly;Tabi, Zsuzsanna
通讯作者：
Tabi, Zsuzsanna
影响因子：
64.8
作者：
Dominguez-Sola, David;Ying, Carol Y.;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
影响因子：
4.4
作者：
Almand, B;Clark, JI;Gabrilovich, DI
通讯作者：
Gabrilovich, DI
DOI：
10.1073/pnas.0600213103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Chen, Kevin G.;Valencia, Julio C.;Gottesman, Michael M.
通讯作者：
Gottesman, Michael M.