一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
英文原题:Neoantigen-based dendritic cell vaccines in lung cancer: overcoming immunosuppressive barriers for durable antitumor immunity.
Neoantigen-based dendritic cell vaccines in lung cancer: overcoming immunosuppressive barriers for durable antitumor immunity.
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基于肿瘤免疫逃逸机制开发的癌症免疫疗法是癌症治疗史上的重大突破,能够通过免疫检查点阻断逆转肿瘤诱导的 T 细胞耗竭。
基于肿瘤免疫逃逸机制开发的癌症免疫疗法是癌症治疗史上的重大突破,能够通过免疫检查点阻断逆转肿瘤诱导的T细胞耗竭。然而,将T细胞作为抗肿瘤免疫的核心角色而过度关注,可能导致了人们对树突状细胞(DCs)所发挥的关键作用的忽视,而DCs对于激活和引导T细胞靶向肿瘤细胞至关重要。DCs包括一组多样化的抗原呈递细胞,在启动和调节固有免疫及适应性免疫应答中发挥着不可或缺的作用。因此,旨在调控DC功能以增强癌症免疫治疗的策略具有至关重要的意义。除了开发新型免疫检查点抑制剂外,基于新抗原的DC疫苗是开发个性化精准免疫治疗的一种有前景的方法。在此,我们综述了肺肿瘤微环境中DC免疫抑制的分子机制、肿瘤浸润DCs如何在癌症环境中影响免疫与耐受、肿瘤特异性新抗原引发免疫应答的机制、新抗原的鉴定,以及新抗原靶向疫苗用于肺癌的最新临床进展。我们还讨论了基于DC疫苗的癌症免疫治疗在临床前研究和临床试验中的最新进展。
Cancer immunotherapies developed based on mechanisms of tumour immune evasion represent a major breakthrough in the history of cancer treatment, capable of reversing T-cell exhaustion induced by tumours through immune checkpoint blockade. However, the predominant focus on T cells as central players in antitumour immunity may have led to the oversight of the crucial role played by dendritic cells (DCs), which are essential for activating and directing T cells against tumour cells. DCs comprise a diverse group of antigen-presenting cells that play an indispensable role in initiating and regulating both innate and adaptive immune responses. Strategies aimed at modulating DC function to enhance cancer immunotherapy are therefore of critical importance. Beyond the development of novel immune checkpoint inhibitors, neoantigen-based DC vaccines represent a promising approach for developing personalised precision immunotherapies. Here, we review the molecular mechanisms underlying DC immunosuppression within the lung tumour microenvironment, how tumour-infiltrating DCs influence immunity and tolerance in the cancer setting, the mechanisms by which tumour-specific neoantigens elicit immune responses, the identification of neoantigens, and recent clinical advances in neoantigen-targeted vaccines for lung cancer. We also discuss recent progress in DC vaccine-based cancer immunotherapies from both preclinical studies and clinical trials.
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