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:Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.
Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.
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嵌合抗原受体(CAR)T 细胞治疗通过识别特定抗原实现对肿瘤的高特异性靶向,是免疫治疗领域发展最快的方式之一,并已在血液系统恶性肿瘤中取得显著成功。然而,早期 CAR-T 细胞治疗用于实体瘤时面临诸多挑战,例如缺乏合适靶点、免疫抑制程度高、细胞持久性不足,以及受肿瘤微环境复杂性影响而浸润不足,这些因素均限制了疗效。本综述聚焦第四代 CAR-T 细胞(亦称装甲 CAR-T 细胞)的当前治疗靶点,并探讨这些工程化细胞如何通过靶向肿瘤微环境的不同组分来应对其影响。为 CAR-T 细胞引入这些治疗靶点有望提高其对实体瘤的疗效,产生重要临床价值并推动 CAR-T 细胞治疗领域发展。此外,我们讨论了克服现有挑战的潜在策略,并介绍可能进一步增强 CAR-T 细胞治疗实体瘤疗效的新靶点。
Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies.
However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy.
In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy.
Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.
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