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嵌合抗原受体(CAR)-T细胞疗法在肾细胞肿瘤中的潜在应用

Potential Application of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Renal Cell Tumors.

作者信息

Schepisi Giuseppe, Conteduca Vincenza, Casadei Chiara, Gurioli Giorgia, Rossi Lorena, Gallà Valentina, Cursano Maria Concetta, Brighi Nicole, Lolli Cristian, Menna Cecilia, Farolfi Alberto, Burgio Salvatore Luca, Altavilla Amelia, Martinelli Giovanni, De Giorgi Ugo

机构信息

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meldola, Italy.

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meldola, Italy.

出版信息

Front Oncol. 2020 Sep 23;10:565857. doi: 10.3389/fonc.2020.565857. eCollection 2020.

Abstract

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CAR-T cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CAR-T cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CAR-T cell therapy in renal cell malignancies.

摘要

目前,肾细胞癌的特点是免疫疗法带来了令人鼓舞的益处,在治疗效果方面取得了显著成果。纳武单抗最初获批作为二线单药治疗,最近新的联合疗法获批作为一线治疗,这证实了免疫疗法在这类肿瘤中的重要性。在此背景下,嵌合抗原受体(CAR)-T细胞疗法在免疫治疗领域向前迈进了一步。这种新的治疗方法最初在血液系统恶性肿瘤中进行测试,目前也成为实体瘤领域备受关注的话题。尽管该疗法相对于先前依赖T细胞受体的免疫疗法有诸多优势,但在实体瘤中仍面临一些障碍,如恶劣的肿瘤微环境和肿瘤内/肿瘤外毒性。目前正在研究多种策略来克服这些问题,但CAR-T细胞疗法的获批仍有一段距离。在肾癌中,免疫检查点抑制剂取得的显著优势是一个良好的起点,但CAR-T细胞疗法潜在的肾脏毒性是一个重要风险。在本综述中,我们阐述了CAR-T细胞疗法用于肾细胞恶性肿瘤治疗的基本原理和初步结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc0a/7538692/40ba171701f9/fonc-10-565857-g001.jpg

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