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:Conversion of primary liver cancer after targeted therapy for liver cancer combined with AFP-targeted CAR T-cell therapy: a case report.
原发性肝癌(PLC)是起源于肝脏的恶性肿瘤,预后最差。
原发性肝癌(PLC)是起源于肝脏的恶性肿瘤,预后最差。肝细胞癌(HCC)是PLC最常见的类型。大多数PLC病例确诊时已处于晚期,主要由于其起病隐匿、进展迅速。PLC患者接受手术干预或局部治疗,但其生存率常受高复发率影响。药物治疗是肝癌患者的主要选择,尤其是伴有晚期肝外转移的患者。分子靶向治疗通过作用于分子发病机制中涉及的多种信号通路发挥抗肿瘤作用;然而,PLC对分子靶点的高耐药性和低治疗反应性使该治疗选择面临挑战。近年来,在手术干预、放疗、化疗和/或分子靶向治疗之后,自体细胞免疫治疗已被用于PLC。作为典型的自体细胞免疫治疗,CAR T细胞疗法利用基因修饰的T细胞表达肿瘤特异性嵌合抗原受体(CAR)。其靶向能力、持久性和杀瘤功能对血液肿瘤的治疗产生了显著影响。然而,针对肺癌、肝癌、乳腺癌及其他常见实体瘤的治疗研究尚未取得突破。在此背景下,采用分子靶向治疗与CAR T细胞疗法联合治疗一名晚期HCC患者,实现了部分缓解(PR)并促进了进一步肝移植。
Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.
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