CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The role of immunotherapy sensitizers and novel immunotherapy modalities in the treatment of cancer.
The role of immunotherapy sensitizers and novel immunotherapy modalities in the treatment of cancer.
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免疫系统在抗癌应答中的重要作用一直是研究热点。免疫检查点抑制剂的出现改变了肿瘤治疗格局,也加深了对癌症病理生理的认识。因此,针对免疫应答不同环节和通路的多种疗法正在研究中。免疫增敏剂应运而生,旨在利用免疫疗法之间,或免疫疗法与化疗、放疗等其他治疗方式联合产生的协同效应。与此同时,新型免疫疗法也在开发中,包括针对肿瘤内在通路、肿瘤微环境及体外干预的策略,如CAR-T 细胞和TIL(肿瘤浸润淋巴细胞)。尽管许多干预最初被设想为单独治疗,但早期体外研究和临床试验显示,联合治疗很有前景。将不同免疫疗法彼此联合,或与其他技术组合,进一步强化了增敏剂理念,有助于在癌症治疗中取得更深入、更稳健的应答。本综述概述免疫治疗联合及其与多种治疗策略联合产生协同效应的增敏机制,并介绍新型免疫疗法,重点讨论其与增敏干预联合的潜力。理解这些原则背后的复杂机制,可能是未来实现突破并改善患者结局的关键。
The importance of the immune system in the response against cancer has always been a subject of intense investigation. The advent of immune checkpoint inhibitors has transformed the landscape of oncologic treatments, while expanding the understanding of this disease's pathophysiology. Consequently, many therapies are being investigated, with interventions directed at different steps and pathways of the immune response. Relevantly, immunotherapy sensitizers have arisen as approaches focused on the synergistic effects of immunotherapy combination, or the combination of immunotherapy and other treatment modalities, such as chemotherapy or radiation therapy. Concomitantly, novel immunotherapy modalities are also in development. Approaches focusing from the tumor intrinsic pathways to the tumor microenvironment and ex-vivo interventions, such as CAR-T cell therapies and tumor-infiltrating lymphocytes are important examples.
Although many of those interventions were initially envisioned as standalone options, their combination has demonstrated promising results in early-phase in vitro studies and clinical trials. The possibility of coupling different immunotherapy modalities, as well as with other techniques, further strengthen the concept of sensitizers, allowing for deeper and more robust responses in cancer treatment.
This review aims to present an overview of the concepts of these sensitizing mechanisms that are the basis for the synergistic effects of immunotherapy combination, or the combination of immunotherapy and a multitude of therapeutic strategies. Novel immunotherapy modalities are also presented, focusing on the potential of combining them with sensitizer interventions. Understanding the complexity underlying these principles may be the key for future breakthroughs and improved patient outcomes.
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