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:The next frontier in immunotherapy: potential and challenges of CAR-macrophages.
嵌合抗原受体巨噬细胞(CAR-M)代表了免疫疗法的重大进步,特别是在治疗传统 CAR-T 疗法面临局限的实体瘤方面。
嵌合抗原受体巨噬细胞(CAR-M)代表了免疫治疗的一项重大进展,尤其是在传统 CAR-T 疗法面临局限的实体瘤治疗中。CAR-M 通过利用巨噬细胞的吞噬和抗原呈递能力,为靶向和清除肿瘤细胞提供了一种有前景的方法。然而,复杂的肿瘤微环境(TME)、抗原表达的可变性以及免疫抑制等挑战限制了其疗效。本综述针对这些问题,探讨了 CAR-M 的作用机制、最优构建体设计以及在 TME 中的相互作用。本综述还深入探讨了 CAR-M 的体外制造挑战,讨论了自体来源和异体来源以及严格质量控制的重要性。本文审视了将 CAR-M 与现有癌症疗法(如检查点抑制剂和常规化疗药物)整合的潜在协同效应,以突出可能改善的治疗结局。此外,本综述还结合 CAR-T 细胞的既定方案,审视了 CAR-M 疗法的监管路径,识别了临床试验和市场批准所必需的独特考量因素。所提出的安全性监测框架旨在管理潜在不良事件,如细胞因子释放综合征,这对患者安全至关重要。本综述整合当前研究和临床见解,旨在完善 CAR-M 治疗应用、克服障碍,并提出未来研究方向,以推动 CAR-M 疗法从实验平台转变为标准癌症治疗选择。
Chimeric antigen receptor macrophage (CAR-M ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-M offers a promising approach to target and eradicate tumor cells by utilizing macrophages' phagocytic and antigen-presenting abilities. However, challenges such as the complex tumor microenvironment (TME), variability in antigen expression, and immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of CAR-M action, optimal construct designs, and interactions within the TME. It also delves into the ex vivo manufacturing challenges of CAR-M , discussing autologous and allogeneic sources and the importance of stringent quality control. The potential synergies of integrating CAR-M with existing cancer therapies like checkpoint inhibitors and conventional chemotherapeutics are examined to highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways for CAR-M therapies are scrutinized alongside established protocols for CAR-T cells, identifying unique considerations essential for clinical trials and market approval. Proposed safety monitoring frameworks aim to manage potential adverse events, such as cytokine release syndrome, crucial for patient safety. Consolidating current research and clinical insights, this review seeks to refine CAR-M therapeutic applications, overcome barriers, and suggest future research directions to transition CAR-M therapies from experimental platforms to standard cancer care options.
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