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:Pancreatic Cancer: Pathogenesis and Clinical Studies.
胰腺癌(PC)是一种高度致命的恶性肿瘤,其中胰腺导管腺癌(PDAC)是最常见且最具侵袭性的亚型,以诊断晚、进展迅速和对常规治疗耐药为特征。
胰腺癌(PC)是一种高度致死的恶性肿瘤,其中胰腺导管腺癌(PDAC)最常见且侵袭性最强,特征为诊断晚、进展迅速、对常规疗法耐药。尽管对其发病机制的认识不断加深,包括识别常见基因突变[如 KRAS、TP53、CDKN2A、SMAD4]及失调信号通路[如 KRAS-MAPK、PI3K-AKT 和 TGF-β 通路],有效治疗策略仍然有限。目前的化疗、靶向治疗、免疫治疗和放疗,以及 ADC、CAR-T 细胞、溶瘤病毒(OV)、癌症疫苗和双特异性抗体(BsAb)等新兴疗法,均面临重大挑战。本综述全面总结这些治疗方法,强调其作用机制、局限和潜在解决方案,以克服治疗瓶颈。通过整合近期进展并概述关键挑战,本文旨在为未来方向提供见解,并指导开发更有效的 PC 治疗策略,特别聚焦 PDAC。研究强调迫切需要应对 PDAC 治疗未满足的需求,并指出该领域具有创新潜力的方向。
Pancreatic cancer (PC) is a highly lethal malignancy, with pancreatic ductal adenocarcinoma (PDAC) being the most common and aggressive subtype, characterized by late diagnosis, aggressive progression, and resistance to conventional therapies. Despite advances in understanding its pathogenesis, including the identification of common genetic mutations (e.g., KRAS, TP53, CDKN2A, SMAD4) and dysregulated signaling pathways (e.g., KRAS-MAPK, PI3K-AKT, and TGF- pathways), effective therapeutic strategies remain limited. Current treatment modalities including chemotherapy, targeted therapy, immunotherapy, radiotherapy, and emerging therapies such as antibody-drug conjugates (ADCs), chimeric antigen receptor T (CAR-T) cells, oncolytic viruses (OVs), cancer vaccines, and bispecific antibodies (BsAbs), face significant challenges. This review comprehensively summarizes these treatment approaches, emphasizing their mechanisms, limitations, and potential solutions, to overcome these bottlenecks. By integrating recent advancements and outlining critical challenges, this review aims to provide insights into future directions and guide the development of more effective treatment strategies for PC, with a specific focus on PDAC. Our work underscores the urgency of addressing the unmet needs in PDAC therapy and highlights promising areas for innovation in this field.
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