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:From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.
胶质母细胞瘤是一种罕见且高度致命的脑癌,在治疗耐药以及成人和儿童患者生存率低方面都带来重大挑战。
胶质母细胞瘤是一种罕见且致死率极高的脑癌,成人和儿童患者均面临治疗耐药及生存率低等重大挑战。尽管脑癌研究因技术革命而不断进步,将对胶质母细胞瘤发病机制的认识转化为临床结局改善,仍是重要的未满足需求。本文重点讨论受体酪氨酸激酶信号通路、表观遗传机制和代谢功能在胶质母细胞瘤发生及治疗耐药中的复杂作用,并综述过去20年来针对这些通路开展靶向治疗的广泛努力。抗体-毒素偶联物或CAR-T细胞疗法等新兴策略通过特异性靶向胶质母细胞瘤细胞表面蛋白,展现潜在价值。将蛋白靶向疗法与免疫疗法结合的策略为未来临床研究带来希望。此外,深入了解胶质母细胞瘤起源细胞对治疗应答的影响,有望推动精准医疗。解决这些挑战对改善患者结局、推进更有效的精准治疗至关重要。
Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.
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