决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Engineered CAR-T and novel CAR-based therapies to fight the immune evasion of glioblastoma: gutta cavat lapidem.
随着CAR T细胞疗法的逐步广泛应用,治疗实体瘤(包括中枢神经系统(CNS)肿瘤)方面的重大挑战正在显现,突出表现为疾病早期复发和癌细胞耐药问题,这归因于不利的免疫抑制微环境和肿瘤抗原异质性。
引言:通过应用表达嵌合抗原受体(CAR)的基因工程T细胞,癌症免疫治疗取得重大进展;这类疗法已成功清除血液系统恶性肿瘤,并在治疗胶质母细胞瘤(GBM)时显示安全性和令人鼓舞的早期抗肿瘤活性。综述范围:讨论CAR-T细胞在GBM中的应用,重点关注限制其进一步发展的障碍,主要包括毒性、恶劣的肿瘤微环境、CAR-T细胞浸润和持续存在能力不足、靶抗原丢失/异质性以及运输至肿瘤部位不足。此外,介绍旨在增强CAR-T活性的优化策略,并探讨用于优化GBM抗肿瘤效果的新型免疫疗法,例如CAR-NK或CAR巨噬细胞(CAR-M)的潜在应用。专家观点:随着CAR-T细胞疗法逐渐广泛应用,实体瘤(包括中枢神经系统〔CNS〕肿瘤)治疗中的重大挑战日益显现,包括早期疾病复发和癌细胞耐药;这些问题源于恶劣的免疫抑制微环境和肿瘤抗原异质性。除CAR-T细胞外,人们也十分关注将其他CAR疗法用于CNS肿瘤,例如CAR自然杀伤(CAR-NK)细胞或CAR巨噬细胞(CAR-M)。
INTRODUCTION: 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). AREAS COVERED: 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. EXPERT OPINION: 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.
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