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:Natural killer and CAR-NK cell therapies in urological cancers: Progress, mechanistic lessons from CAR-T, and future directions.
我们得出结论:尽管 CAR-NK 疗法是治疗这些癌症的一种有前景的「即用型」手段,但其在实体瘤中的成功取决于下一代设计,这些设计需解决体内持久性、高效肿瘤归巢以及抵抗局部代谢与免疫抑制压力等关键挑战。
本综述总结自然杀伤(NK)和嵌合抗原受体NK(CAR-NK)细胞疗法治疗泌尿系统肿瘤(包括肾细胞癌、膀胱癌和前列腺癌)的现有进展、挑战及未来方向。文章介绍NK细胞独特生物学特征,如“缺失自身”识别及内在抗体依赖性细胞毒作用(ADCC),这些特性可能使其相较CAR-T具有安全性和疗效优势,包括重度细胞因子释放综合征和移植物抗宿主病风险较低。分析涵盖传统NK细胞策略、CAR-NK平台工程化和“装甲化”以克服免疫抑制性肿瘤微环境,以及针对CAIX、CD70、PSMA和nectin-4等抗原治疗不同泌尿系统恶性肿瘤的临床前和早期临床进展。综述认为,CAR-NK有望成为治疗这些癌症的“现货型”方式,但其实体瘤疗效取决于新一代设计能否解决体内持续性、有效肿瘤归巢,以及抵抗局部代谢和免疫抑制压力等关键问题。
This review aims to synthesize the current progress, challenges, and future directions of Natural Killer (NK) and Chimeric Antigen Receptor-NK (CAR-NK) cell therapies for urological cancers, including renal cell carcinoma, bladder cancer, and prostate cancer. We detail the unique biology of NK cells, such as 'missing-self' recognition and intrinsic antibody-dependent cellular cytotoxicity (ADCC), which offer potential safety and efficacy advantages over CAR-T cells, including a lower risk of severe cytokine release syndrome and graft-versus-host disease. The analysis covers conventional NK-based strategies, the engineering and 'armouring' of CAR-NK platforms to overcome the immunosuppressive tumour microenvironment, and preclinical and early clinical advances with target antigens like CAIX, CD70, PSMA, and nectin-4 across different urological malignancies. We conclude that while CAR-NK therapy represents a promising 'off-the-shelf' modality for these cancers, its success in solid tumours hinges on next-generation designs that solve critical challenges of in vivo persistence, efficient tumour homing, and resistance to local metabolic and immunosuppressive pressures.
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