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 current landscape of optogenetics for the enhancement of adoptive T-cell therapy.
The current landscape of optogenetics for the enhancement of adoptive T-cell therapy.
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免疫疗法,即通过药物调节宿主免疫反应以更好地对抗病原体或疾病,近几十年来已彻底改变了癌症治疗。T细胞作为适应性免疫系统的重要组成部分,对治疗成功尤为关键。
因此,近期的免疫治疗模式更频繁地靶向T细胞用于癌症治疗及其他病理状况,被称为过继性T细胞(ATC)疗法。ATC疗法涵盖多种类型的免疫治疗,但主要归属于三种成熟技术:TIL(肿瘤浸润淋巴细胞)、CAR-T 细胞和工程化T细胞受体疗法。尽管临床结果令人鼓舞,但所有ATC疗法类型在提供长期持续的肿瘤清除方面均存在不足,同时对实体瘤尤其无效,大量研究致力于理解和预防ATC疗法的典型缺陷。光遗传学是一项相对较新的进展,其将光敏蛋白结构域整合到目标细胞或组织中,以光学方式调控特定生物学过程。光遗传学操控免疫功能正迅速成为免疫学中的研究工具,光敏系统现已被用于优化多种细胞治疗模式和ATC疗法。本综述聚焦于光遗传学方法目前如何通过加深我们对治疗成功背后分子机制的理解,来改善临床环境中的ATC疗法。
此外,本综述进一步评述了当前的免疫光遗传学系统,并对近期发展的扩展进行了展望,以增强当前基于ATC的治疗模式,为临床进展铺平道路。
Immunotherapy, the medicinal modulation of a host's immune response to better combat a pathogen or disease, has transformed cancer treatments in recent decades. T-cells, an important component of the adaptive immune system, are further paramount for therapy success. Recent immunotherapeutic modalities have therefore more frequently targeted T-cells for cancer treatments and other pathologies and are termed adoptive T-cell (ATC) therapies. ATC therapies characterize various types of immunotherapies but predominantly fall into three established techniques: tumour-infiltrating lymphocyte, chimeric antigen receptor T-cell, and engineered T-cell receptor therapies.
Despite promising clinical results, all ATC therapy types fall short in providing long-term sustained tumour clearance while being particularly ineffective against solid tumours, with substantial developments aiming to understand and prevent the typical drawbacks of ATC therapy. Optogenetics is a relatively recent development, incorporating light-sensitive protein domains into cells or tissues of interest to optically tune specific biological processes.
Optogenetic manipulation of immunological functions is rapidly becoming an investigative tool in immunology, with light-sensitive systems now being used to optimize many cellular therapeutic modalities and ATC therapies. This review focuses on how optogenetic approaches are currently utilized to improve ATC therapy in clinical settings by deepening our understanding of the molecular rationale behind therapy success.
Moreover, this review further critiques current immuno-optogenetic systems and speculates on the expansion of recent developments, enhancing current ATC-based therapeutic modalities to pave the way for clinical progress.
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