Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2C1, Canada.
Division of Neurology, Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
Curr Oncol. 2023 Sep 15;30(9):8501-8549. doi: 10.3390/curroncol30090619.
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.
胶质母细胞瘤是成人中最常见的恶性原发性脑肿瘤。即使采用最大安全切除、放疗和化疗的标准治疗，预后也极差。在数月内不可避免地会复发，并且治疗选择非常有限。嵌合抗原受体 T 细胞疗法 (CART) 和双特异性 T 细胞衔接器 (TCE) 是两种新兴的免疫疗法，可将 T 细胞重新定向用于肿瘤特异性杀伤，在血液恶性肿瘤中取得了显著成功，并正在广泛研究其在胶质母细胞瘤中的应用。虽然有多项临床试验初步证明了 CART 的安全性和疗效，但双特异性 TCE 仍处于临床测试的早期阶段，临床前研究显示出非常有前途的结果。然而，未来仍需要解决多个共同的挑战，包括给药途径、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治疗方法的设计，并寻找理想的联合治疗方法来克服这些挑战。在这篇综述中，我们描述了已经完成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。
