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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engineered CAR-T cells: An immunotherapeutic approach for cancer treatment and beyond.
Engineered CAR-T cells: An immunotherapeutic approach for cancer treatment and beyond.
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嵌合抗原受体(CAR)T 细胞疗法是一种过继免疫疗法,可望增强癌症治疗效果,因为尽管化疗、手术和放疗取得了相对积极结果,仍无法彻底清除肿瘤。CAR-T 已显示出治疗多数血液系统恶性肿瘤的良好结果,并有望拓展至其他癌症类型。CAR 是 T 细胞上的额外受体,可高效活化免疫系统,增强和加速肿瘤清除。CAR 由三个结构域组成:胞外结构域、跨膜结构域和胞内结构域。胞外结构域对抗原识别和结合至关重要;胞内结构域则传递共刺激信号。截至目前,美国食品药品监督管理局(FDA)已批准 6 种 CAR-T 疗法。尽管 CAR-T 取得显著成功,仍伴有多种不良事件和一定局限。本章聚焦 CAR 结构域的结构与功能、CAR 的不同代次、CAR-T 的开发流程、不良反应和治疗挑战。CAR-T 也可能用于其他疾病,包括系统性红斑狼疮、多发性硬化和心肌纤维化等。
Chimeric Antigen Receptor (CAR) T cell therapy is a type of adoptive immunotherapy that offers a promising avenue for enhancing cancer treatment since traditional cancer treatments like chemotherapy, surgery, and radiation therapy have proven insufficient in completely eradicating tumors, despite the relatively positive outcomes. It has been observed that CAR-T cell therapy has shown promising results in treating the majority of hematological malignancies but also have a wide scope for other cancer types.
CAR is an extra receptor on the T-cell that helps to increase and accelerate tumor destruction by efficiently activating the immune system. It is made up of three domains, the ectodomain, transmembrane, and the endodomain. The ectodomain is essential for antigen recognition and binding, whereas the co-stimulatory signal is transduced by the endodomain. To date, the Food and Drug Administration (FDA) has granted approval for six CAR-T cell therapies.
However, despite its remarkable success, CAR-T therapy is associated with numerous adverse events and has certain limitations. This chapter focuses on the structure and function of the CAR domain, various generations of CAR, and the process of CAR-T cell development, adverse effects, and challenges in CAR-T therapy. CAR-T cell therapy also has scopes in other disease conditions which include systemic lupus erythematosus, multiple sclerosis, and myocardial fibrosis, etc.
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