为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Rapidly Evolving Landscape and Future Horizons in Hepatocellular Carcinoma in the Era of Immuno-Oncology.
Rapidly Evolving Landscape and Future Horizons in Hepatocellular Carcinoma in the Era of Immuno-Oncology.
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肝细胞癌(HCC)是一个严重的全球健康问题,是全球癌症相关死亡的主要原因之一。随着分子靶向药物的开发,晚期HCC的系统治疗取得了进展,但生存获益仍然有限。最近,免疫检查点抑制剂(ICI)已经出现,并在部分患者中显示出有希望的治疗获益。在生理上,肝脏固有的微环境具有免疫抑制作用,这是原发性和继发性肝脏恶性肿瘤有效免疫治疗的主要障碍。因此,能够克服免疫抑制机制并增强免疫反应的联合治疗是HCC药物开发的合理方法。最近的一个例子是抗PD-L1抗体(atezolizumab)和抗VEGF-A抗体(bevacizumab)的联合治疗,与HCC一线治疗的标准治疗相比,该联合治疗已显示出显著的生存改善。其他免疫治疗方法包括癌症疫苗和过继细胞疗法也正在研究中。本综述总结了导致我们当前HCC治疗选择的关键试验,并概述了正在开发中的未来基于免疫的策略。
Hepatocellular carcinoma (HCC) is a serious global health problem as one of the leading causes of cancer-related death worldwide. Systemic therapy for advanced HCC has progressed with the development of molecular targeted agents, however survival benefits remain modest. More recently, immune checkpoint inhibitors (ICI) have emerged and exhibited promising therapeutic benefits in a subset of patients. Physiologically, the intrinsic microenvironment in the liver is immunosuppressive, which represents a major obstacle for effective immune therapies in primary and secondary liver malignancies.
For this reason, combination therapies that can overcome immune inhibitory mechanisms and enhance the immune response are a rationale approach for drug development in HCC. A recent example is the combination of the anti-PD-L1 antibody (atezolizumab) and anti-VEGF-A antibody (bevacizumab), which has shown significant improvement in survival as compared to standard of care in the first-line treatment for HCC.
Other immunotherapy approaches including cancer vaccines and adoptive cell therapy are also under investigation. This review summarizes the key trials leading to our current HCC treatment options and provides an overview of future immune-based strategies in development.
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