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硫酸软骨素蛋白聚糖4作为靶标的CAR-T细胞免疫治疗实体肿瘤

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发表于 2015-12-23 21:53:38 | 显示全部楼层 |阅读模式
Chondroitin sulfate proteoglycan 4 as a target for chimeric antigen receptor-based T-cell immunotherapy of solid tumors.
L
INTRODUCTION:
Proteoglycans are critical molecules involved in multiple physiological cell functions, but also key players in cancer development and progression. In particular, chondroitin sulfate proteoglycan 4 (CSPG4) is recognized as an attractive target for antibody-based approaches because of its high expression on cancer cells in several types of human malignancies and its restricted distribution in normal tissues.
AREAS COVERED:
Adoptive transfer of genetically modified T cells is emerging as a powerful therapeutic approach in cancer patients. In this regard, the selection of the appropriate antigen to be targeted in solid tumors becomes a critical aspect in promoting potent antitumor effects while preventing toxicities. This review summarizes the authors' current knowledge on the expression and function of CSPG4 in normal tissues and malignant tumors, with a particular focus on the potential use of CSPG4 as a target for antigen-specificity redirected T cells.
EXPERT OPINION:
T cells expressing a CSPG4-specific chimeric antigen receptor (CAR) offer the possibility to target a broad spectrum of solid tumors for which no curative treatment is currently available. In addition, since CSPG4 is also selectively up-regulated on tumor-associated pericytes, targeting this antigen may also contribute to tumor regression via inhibition of neoangiogenesis. Preclinical experiments to date justify the clinical translation of CSPG4-specific CAR-T cells.
硫酸软骨素蛋白聚糖4作为靶标的CAR-T细胞免疫治疗实体肿瘤
介绍
蛋白多糖是一个重要参与多种生理细胞功能的分子,在肿瘤的发生和发展过程中扮演了非常重要的角色。特别是硫酸软骨素蛋白聚糖4,它被公认为一个基于抗原治疗的一个活性分子,因为它在多种癌细胞表面大量表达,而在普通正常组织中表达有限。
覆盖区域
基因修饰的过继T细胞治疗的出现,对于癌症病人而言是一个非常强大的治疗方式。在这方面,肿瘤表面合适的抗原的选择是一个非常关键的因素,不仅能够促进对肿瘤的杀灭活性,也能组织毒副作用的产生。这篇文章总结了CSPG4在正常组织和肿瘤组织表面的表达和功能。主要讨论了使用CSPG4作为靶标的CAR-T细胞技术的应用潜力。
专家意见
靶向CSPG4CAR-T细胞治疗为目前没有可用治疗的实体肿瘤病人扩大了治疗手段。此外,自从CSPG4在肿瘤相关细胞表面表达上调,可能通过移植周围血管的生成来抑制肿瘤的生长。到目前为止的临床移植都证明了CSPG4 CAR-T细胞的有效性。
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