Haydar Dalia, Ibañez-Vega Jorge, Krenciute Giedre
Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, United States.
Front Oncol. 2021 Oct 25;11:718030. doi: 10.3389/fonc.2021.718030. eCollection 2021.
Despite decades of research, pediatric central nervous system (CNS) tumors remain the most debilitating, difficult to treat, and deadliest cancers. Current therapies, including radiation, chemotherapy, and/or surgery, are unable to cure these diseases and are associated with serious adverse effects and long-term impairments. Immunotherapy using chimeric antigen receptor (CAR) T cells has the potential to elucidate therapeutic antitumor immune responses that improve survival without the devastating adverse effects associated with other therapies. Yet, despite the outstanding performance of CAR T cells against hematologic malignancies, they have shown little success targeting brain tumors. This lack of efficacy is due to a scarcity of targetable antigens, interactions with the immune microenvironment, and physical and biological barriers limiting the homing and trafficking of CAR T cells to brain tumors. In this review, we summarize experiences with CAR T-cell therapy for pediatric CNS tumors in preclinical and clinical settings and focus on the current roadblocks and novel strategies to potentially overcome those therapeutic challenges.
尽管经过了数十年的研究，小儿中枢神经系统（CNS）肿瘤仍然是最具致残性、最难治疗且最致命的癌症。目前的治疗方法，包括放疗、化疗和/或手术，无法治愈这些疾病，并且会带来严重的副作用和长期损伤。使用嵌合抗原受体（CAR）T细胞的免疫疗法有可能引发治疗性抗肿瘤免疫反应，从而提高生存率，且不会产生与其他疗法相关的毁灭性副作用。然而，尽管CAR T细胞在治疗血液系统恶性肿瘤方面表现出色，但它们在靶向脑肿瘤方面却收效甚微。这种疗效不佳是由于可靶向抗原的稀缺、与免疫微环境的相互作用，以及限制CAR T细胞归巢和向脑肿瘤迁移的物理和生物学屏障。在这篇综述中，我们总结了CAR T细胞疗法在小儿中枢神经系统肿瘤临床前和临床环境中的经验，并重点关注当前的障碍以及可能克服这些治疗挑战的新策略。
