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:Current Status of Drug Treatment of Cholangiocarcinoma-Updated Progress and Critical Limitations.
胆管癌(CCA)是一种起源于胆道系统的高度致死性、异质性恶性肿瘤。
胆管癌(CCA)是一种起源于胆道系统的高度致死性、异质性恶性肿瘤。尽管CCA的患病率相对较低,但近几十年来其发病率有所上升,且总体预后较差。手术切除仍是CCA最有效的治疗方式。然而,由于其侵袭性强且常无明显症状,大多数患者初诊时即为晚期,无法接受根治性干预。此外,由于其在分子、基因组和表观遗传层面的异质性,CCA的药物治疗仍面临挑战。在本综述中,我们讨论CCA当前的标准药物治疗方案、近期突破以及有前景的新型治疗手段。我们总结标准一线化疗方案的关键临床数据及其疗效和耐药机制,以及支持或提出二线治疗的较新研究。我们重点介绍具有里程碑意义的临床试验,包括ABC-02,该试验确立了吉西他滨-顺铂(GC)作为胆道癌一线方案。此外,我们讨论关于CCA对靶向治疗和其他免疫分子敏感性的近期发现,包括KEYNOTE-966和TOPAZ-1临床试验的结果。最后,我们批判性分析临床前和临床阶段的新疗法,如可能对CCA有效的CAR-T细胞和溶瘤病毒。
Cholangiocarcinoma (CCA) is a highly lethal, heterogeneous malignancy arising from the biliary tract. Although the prevalence of CCA is relatively low, its incidence has increased in the last few decades, and the overall prognosis is poor. Surgical resection remains the most efficacious treatment modality for CCA. However, due to its aggressive nature and often asymptomatic presentation, most patients are first diagnosed with advanced disease, precluding them from curative intervention. Moreover, due to its heterogeneity at the molecular, genomic, and epigenetic levels, drug treatment of CCA remains challenging. In this review, we discuss the current standard drug treatment approaches, recent breakthroughs, and promising new therapeutics for CCA. We summarize key clinical data for the standard first-line chemotherapy regimen and its efficacy and resistance mechanisms, along with more recent studies supporting or proposing second-line treatments. We highlight landmark clinical trials, including ABC-02, which established gemcitabine-cisplatin (GC) as the first-line regimen against biliary cancers. Additionally, we discuss recent findings on the susceptibility of CCA against targeted therapies and other immunologic molecules, including results from the KEYNOTE-966 and TOPAZ-1 clinical trials. Finally, we critically analyze new therapeutics in the preclinical and clinical space, such as CAR-T cells and oncolytic viruses that may be effective against CCA.
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