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:To go or not to go? Biological logic gating engineered T cells.
To go or not to go? Biological logic gating engineered T cells.
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基因工程T细胞已成功用于治疗血液系统恶性肿瘤,显著提高了患者的无进展生存期和总生存期。然而,靶向实体瘤的嵌合抗原受体(CAR)T细胞治疗结果令人失望。目前临床迫切需要专门设计用于克服实体瘤相关挑战(如肿瘤异质性和抗原逃逸)的疗法。在T细胞中采用生物逻辑门控的基因工程是一个新兴的前沿领域,可能解决这些问题。逻辑门控的优势包括在肿瘤微环境中局部分泌抗肿瘤蛋白、多抗原靶向肿瘤,以及在靶向可能并非肿瘤特异性的肿瘤抗原时潜在提高安全性。在本综述中,我们介绍生物逻辑门控的概念以及该技术如何解决当前CAR-T 治疗的一些挑战。我们概述逻辑门控回路的类型,最后讨论这项新技术在工程化T细胞治疗癌症中的应用。
Genetically engineered T cells have been successfully used in the treatment of hematological malignancies, greatly increasing both progression-free and overall survival in patients.
However, the outcomes of patients treated with Chimeric Antigen Receptor (CAR) T cells targeting solid tumors have been disappointing. There is an unmet clinical need for therapies which are specifically designed to overcome the challenges associated with solid tumors such as tumor heterogeneity and antigen escape. Genetic engineering employing the use of biological logic gating in T cells is an emerging and cutting-edge field that may address these issues.
The advantages of logic gating include localized secretion of anti-tumor proteins into the tumor microenvironment, multi antigen targeting of tumors and a potential increase in safety when targeting tumor antigens which may not be exclusively tumor specific. In this review, we introduce the concept of biological logic gating and how this technology addresses some of the challenges of current CAR T treatment.
We outline the types of logic gating circuits and finally discuss the application of this new technology to engineered T cells, in the treatment of cancer.
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