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:Chimeric antigen receptor adoptive immunotherapy in central nervous system tumors: state of the art on clinical trials, challenges, and emerging strategies to addressing them.
创新策略旨在克服 TME 和抗原多样性带来的障碍,通过工程化手段及与免疫检查点抑制剂的联合治疗来预防 CAR-T 细胞耗竭,从而改善治疗结局。
中枢神经系统肿瘤具有高死亡率和致残率,治疗需求未满足。CAR-T为改善疗效带来希望,但其在实体瘤及中枢神经系统肿瘤中的效果仍有限,原因包括复杂肿瘤微环境、抗原异质性和CAR-T耗竭。本文综述中枢神经系统肿瘤CAR-T治疗现状、最新进展及疗效障碍。新策略包括改造细胞并与免疫检查点抑制剂联合,以克服微环境和抗原多样性、预防T细胞耗竭。中枢神经系统肿瘤还存在特有神经毒性挑战,需采用专门管理方法,例如建立分级系统、监测设备、替代细胞平台及加入自杀基因。持续研究和临床进展对于克服现存难题、发挥CAR-T治疗潜力至关重要。
PURPOSE OF REVIEW: Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy. RECENT FINDINGS: Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes. SUMMARY: Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.
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