通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
我们的研究结果定义了一个精准溶瘤平台,该平台能够解除TAM介导的免疫抑制,同时增强适应性免疫,为癌症免疫治疗提供了一条有前景的转化途径。
英文原题:Emerging immunotherapy for HCC: A guide for hepatologists.
HCC约占所有原发性肝癌病例的近90%。
HCC是全球最常见的癌症之一,也是全球癌症相关死亡的第三大原因。HCC占所有原发性肝癌病例的近90%。约半数HCC患者在其病程中接受全身治疗,尤其是在疾病晚期阶段。免疫肿瘤学已改变了人类癌症的治疗格局,在包括HCC在内的多种恶性肿瘤中,一部分患者表现出强效且持久的抗肿瘤活性。使用atezolizumab和bevacizumab(一种抗血管内皮生长因子中和抗体)的免疫检查点抑制已成为晚期HCC患者的一线治疗。除免疫检查点抑制外,溶瘤病毒免疫治疗和过继性T细胞转移等免疫治疗策略目前正在研究中。HCC的肿瘤免疫微环境具有显著的免疫抑制成分,可能影响对免疫治疗的反应。尚未解决的主要挑战包括:明确免疫治疗在HCC早期阶段的作用,评估靶向免疫微环境联合免疫检查点抑制的组合策略,以及为对当前可用免疫治疗无反应的患者确定治疗策略。本文中,我们综述了HCC免疫治疗的理论依据、机制基础和支持性临床前证据、现有临床证据以及正在进行的免疫治疗临床试验。
HCC is one of the most common cancers worldwide, and the third leading cause of cancer-related death globally. HCC comprises nearly 90% of all cases of primary liver cancer. Approximately half of all patients with HCC receive systemic therapy during their disease course, particularly in the advanced stages of disease. Immuno-oncology has been paradigm shifting for the treatment of human cancers, with strong and durable antitumor activity in a subset of patients across a variety of malignancies including HCC. Immune checkpoint inhibition with atezolizumab and bevacizumab, an antivascular endothelial growth factor neutralizing antibody, has become first-line therapy for patients with advanced HCC. Beyond immune checkpoint inhibition, immunotherapeutic strategies such as oncolytic viroimmunotherapy and adoptive T-cell transfer are currently under investigation. The tumor immune microenvironment of HCC has significant immunosuppressive elements that may affect response to immunotherapy. Major unmet challenges include defining the role of immunotherapy in earlier stages of HCC, evaluating combinatorial strategies that use targeting of the immune microenvironment plus immune checkpoint inhibition, and identifying treatment strategies for patients who do not respond to the currently available immunotherapies. Herein, we review the rationale, mechanistic basis and supporting preclinical evidence, and available clinical evidence for immunotherapies in HCC as well as ongoing clinical trials of immunotherapy.
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