Medical Oncology Department, Azienda USL, Bologna, Italy.
IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Oncologia Medica del Sistema Nervoso, Bologna, Italy.
Expert Rev Anticancer Ther. 2021 Dec;21(12):1333-1353. doi: 10.1080/14737140.2021.1997599.
The field of cancer immunotherapy has achieved great advancements through the application of genetically engineered T cells with chimeric antigen receptors (CAR), that have shown exciting success in eradicating hematologic malignancies and have proved to be safe with promising early signs of antitumoral activity in the treatment of glioblastoma (GBM).
We discuss the use of CAR T cells in GBM, focusing on limitations and obstacles to advancement, mostly related to toxicities, hostile tumor microenvironment, limited CAR T cells infiltration and persistence, target antigen loss/heterogeneity and inadequate trafficking. Furthermore, we introduce the refined strategies aimed at strengthening CAR T activity and offer insights in to novel immunotherapeutic approaches, such as the potential use of CAR NK or CAR M to optimize anti-tumor effects for GBM management.
With the progressive wide use of CAR T cell therapy, significant challenges in treating solid tumors, including central nervous system (CNS) tumors, are emerging, highlighting early disease relapse and cancer cell resistance issues, owing to hostile immunosuppressive microenvironment and tumor antigen heterogeneity. In addition to CAR T cells, there is great interest in utilizing other types of CAR-based therapies, such as CAR natural killer (CAR NK) or CAR macrophages (CAR M) cells for CNS tumors.
通过应用嵌合抗原受体 (CAR) 基因工程 T 细胞，癌症免疫疗法领域取得了重大进展，这些细胞在消除血液恶性肿瘤方面显示出令人兴奋的成功，并已被证明在治疗胶质母细胞瘤 (GBM) 方面具有安全性和有前途的早期抗肿瘤活性迹象。
我们讨论了 CAR T 细胞在 GBM 中的应用，重点讨论了进展的限制和障碍，主要与毒性、敌对的肿瘤微环境、有限的 CAR T 细胞浸润和持久性、靶抗原丢失/异质性和不足的转移有关。此外，我们介绍了旨在增强 CAR T 活性的精细策略，并提供了对新型免疫治疗方法的见解，例如潜在使用 CAR NK 或 CAR M 来优化 GBM 管理的抗肿瘤效果。
随着 CAR T 细胞疗法的广泛应用，治疗实体瘤（包括中枢神经系统 (CNS) 肿瘤）方面出现了重大挑战，这凸显了早期疾病复发和癌细胞耐药问题，这归因于敌对的免疫抑制微环境和肿瘤抗原异质性。除了 CAR T 细胞外，人们对利用其他类型的基于 CAR 的疗法（例如 CAR 自然杀伤 (CARNK) 或 CAR 巨噬细胞 (CAR M) 细胞）治疗 CNS 肿瘤也非常感兴趣。
