Prospective approaches to enhancing CAR T cell therapy for glioblastoma.
Prospective approaches to enhancing CAR T cell therapy for glioblastoma.
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增强胶质母细胞瘤的汽车T细胞疗法的前瞻性方法。
DOI：
10.3389/fimmu.2022.1008751
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤。目前的标准治疗（包括手术、化疗和放疗）的临床结果不佳和总体无效，突出了对GBM替代肿瘤特异性治疗的迫切需要。嵌合抗原受体（CAR）T细胞疗法是血液恶性肿瘤的革命性治疗策略，但CAR T细胞疗法对实体瘤，特别是GBM的最佳效力尚未实现。尽管已经在临床试验中评估了GBM的CAR T细胞治疗策略，但CAR T细胞目前的抗肿瘤活性仍然不足。在这篇综述中，我们提出了我们对遗传修饰CAR构建体，克服T细胞功能障碍，以及开发可以提高CAR T细胞有效性的其他治疗方法的观点，例如功能性，持久性和肿瘤部位的浸润。有效改善的CAR T细胞可能为GBM患者提供新的治疗机会，本文旨在为研究人员使用基因工程或组合制剂开发有效的CAR T细胞提供全面的概述。
Glioblastoma (GBM) is the most common malignant brain tumor. The poor clinical outcome and overall ineffectiveness of current standard treatments, including surgery, chemotherapy, and radiation, highlight the urgent need for alternative tumor-specific therapies for GBM. Chimeric antigen receptor (CAR) T cell therapy is a revolutionary therapeutic strategy for hematological malignancies, but the optimal potency of CAR T cell therapy for solid tumors, especially GBM, has not been achieved. Although CAR T cell therapeutic strategies for GBM have been assessed in clinical trials, the current antitumor activity of CAR T cells remains insufficient. In this review, we present our perspective on genetically modifying CAR constructs, overcoming T cell dysfunctions, and developing additional treatments that can improve CAR T cell effectiveness, such as functionality, persistence, and infiltration into tumor sites. Effectively improved CAR T cells may offer patients with GBM new treatment opportunities, and this review is intended to provide a comprehensive overview for researchers to develop potent CAR T cells using genetic engineering or combinatorial preparations.