The current landscape of optogenetics for the enhancement of adoptive T-cell therapy.

Discovery immunology Pub Date : 2024-12-23 eCollection Date: 2025-01-01 DOI:10.1093/discim/kyae019
George R Smith, Max P Lee, Emma K Jennings, John R James
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Abstract

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.

光遗传学在增强采用 T 细胞疗法方面的现状。
免疫疗法是对宿主免疫反应进行药物调节以更好地对抗病原体或疾病的一种疗法,近几十年来已经改变了癌症治疗方法。t细胞是适应性免疫系统的重要组成部分,对治疗成功至关重要。因此,最近的免疫治疗方式更频繁地针对t细胞治疗癌症和其他病理,并被称为过继性t细胞(ATC)治疗。ATC疗法具有各种类型的免疫疗法的特点,但主要分为三种已建立的技术:肿瘤浸润淋巴细胞、嵌合抗原受体t细胞和工程t细胞受体疗法。尽管有很好的临床结果,但所有的ATC治疗类型在提供长期持续的肿瘤清除方面都存在不足,同时对实体肿瘤特别无效,旨在了解和预防ATC治疗的典型缺点的重大进展。光遗传学是一项相对较新的发展,将光敏蛋白结构域整合到感兴趣的细胞或组织中,以光调谐特定的生物过程。免疫功能的光遗传学操作正迅速成为免疫学的研究工具,光敏系统现在被用于优化许多细胞治疗方式和ATC治疗。这篇综述的重点是通过加深我们对治疗成功背后的分子原理的理解,目前如何利用光遗传学方法来改善临床环境中的ATC治疗。此外,本综述进一步批评了当前的免疫光遗传系统,并推测了最近发展的扩展,增强了当前基于atc的治疗模式,为临床进展铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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