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双特异性 T 细胞衔接器与 CAR-T 细胞疗法在胶质母细胞瘤中的应用:最新进展

英文原题:Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update.

查看英文原题

Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update.

PubMed 2023/09/15(内容时间) Curr Oncol Q2 · IF 3.6(JCR 2025)

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中文摘要

胶质母细胞瘤是成人中最常见的恶性原发性脑肿瘤。即使采用最大安全范围切除、放疗和化疗的标准治疗,预后仍极差。复发在数月内不可避免,治疗选择非常有限。CAR-T 细胞疗法(CAR-T)和双特异性T细胞衔接器(TCEs)是两种新兴的免疫疗法,能够重定向T细胞以实现肿瘤特异性杀伤,已在血液系统恶性肿瘤中取得显著成功,并正在广泛研究其应用于胶质母细胞瘤的可能性。虽然已有多个临床试验显示CAR-T 的安全性和有效性初步证据,但双特异性TCEs仍处于临床测试的早期阶段,临床前研究显示出非常有希望的结果。然而,未来需要解决多个共同挑战,包括递送途径、抗原逃逸、免疫抑制性肿瘤微环境以及由于肿瘤特异性抗原选择有限而导致的毒性。目前正在努力优化这两种疗法的设计,并寻找理想的联合治疗以克服这些挑战。在本综述中,我们描述了已开展的工作以及在胶质母细胞瘤和其他实体瘤中可能适用于未来的新方法。

展开英文摘要原文

Glioblastoma is the most common malignant primary brain tumor in adults. The prognosis is extremely poor even with standard treatment of maximal safe resection, radiotherapy, and chemotherapy. Recurrence is inevitable within months, and treatment options are very limited.

Chimeric antigen receptor T-cell therapy (CART) and bispecific T-cell engagers (TCEs) are two emerging immunotherapies that can redirect T-cells for tumor-specific killing and have shown remarkable success in hematological malignancies and been under extensive study for application in glioblastoma. While there have been multiple clinical trials showing preliminary evidence of safety and efficacy for CART, bispecific TCEs are still in the early stages of clinical testing, with preclinical studies showing very promising results.

However, there are multiple shared challenges that need to be addressed in the future, including the route of delivery, antigen escape, the immunosuppressive tumor microenvironment, and toxicity resulting from the limited choice of tumor-specific antigens.

Efforts are underway to optimize the design of both these treatments and find the ideal combination therapy to overcome these challenges. In this review, we describe the work that has been performed as well as novel approaches in glioblastoma and in other solid tumors that may be applicable in the future.

论文信息

作者
Alsajjan R、Mason WP
单位
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2C1, Canada.Canada
文献类型
综述
期刊
Current oncology (Toronto, Ont.)2023 Sep 15
原文标识
PubMed 37754534 · DOI 10.3390/curroncol30090619