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:CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.
CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.
胰腺导管腺癌(PDAC)被认为是最致命的恶性肿瘤之一,其特征是预后差且对常规治疗具有显著耐药性。
胰腺导管腺癌(PDAC)被认为是最致命的恶性肿瘤之一,其特点是预后差且对常规治疗具有显著耐药性。尽管嵌合抗原受体(CAR)-T细胞疗法被认为是B细胞恶性肿瘤的革命性治疗方法,但其对包括PDAC在内的实体瘤的疗效有限。然而,经过大量临床前和临床测试,首个针对实体瘤的CAR-T疗法新药申请(NDA)获得受理,这激发了相当大的希望和兴趣,可能进一步加速该领域的发展。要释放CAR-T在PDAC中的全部潜力,需要克服重大障碍,主要是缺乏理想的肿瘤特异性抗原以及深度免疫抑制的肿瘤微环境(TME)。鉴于肿瘤相关抗原(TAA)在多种实体瘤中共享表达,本综述分析了有前景的实体瘤靶点,以识别对PDAC具有高转化可行性的候选靶点。我们总结了CAR-T细胞疗法的最新临床进展,重点介绍了新兴的治疗靶点,并探索了创新工程策略,以开发正在推进未来临床应用的有效、多靶点CAR构建体。
Pancreatic ductal adenocarcinoma (PDAC) is regarded as one of the most lethal malignancies, characterized by a poor prognosis and significant resistance to conventional treatments. Although Chimeric Antigen Receptor (CAR)-T cell therapy has been considered to be a revolutionary treatment for B-cell malignancies, its efficacy against solid tumors, including PDAC, has been limited. Nevertheless, after numerous tests pre-clinically and clinically, the acceptance of the first New Drug Application (NDA) for a CAR-T therapy in a solid tumor has sparked considerable hope and interest, which could further accelerate the field. Unlocking the full potential of CAR-T in PDAC requires overcoming significant hurdles, primarily the lack of ideal tumor-specific antigens and the profoundly immunosuppressive tumor microenvironment (TME). Given the shared expression of tumor-associated antigens (TAAs) across diverse solid tumors, this review analyzes promising solid tumor targets to identify candidates with high translational viability for PDAC. We summarize the latest clinical progress of CAR-T cell therapy, highlight emerging therapeutic targets, and explore innovative engineering strategies for developing potent, multi-targeted CAR constructs that are advancing toward future clinical application.
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