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:CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence.
CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence.
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作为一种新兴的恶性肿瘤治疗策略,CAR-T(CAR-T)细胞疗法已在临床实践中广泛应用,过去十年其疗效显著提高。然而,CAR-T 疗法的临床效果并不尽如人意,尤其是在实体瘤中。即使在血液系统恶性肿瘤中,部分患者在接受CAR-T 细胞输注后最终仍会复发,原因在于CAR-T 细胞扩增和持久性不佳。近年来,CRISPR/Cas9技术为促进CAR-T 细胞在体内的增殖和持久性提供了一种有效途径。该技术已被用于CAR-T 细胞中以产生记忆表型、减少耗竭,并筛选新靶点以提高抗肿瘤潜力。在本综述中,我们旨在描述限制CAR-T 细胞在患者体内持久性的主要原因,并讨论CRISPR/Cas9在促进CAR-T 细胞持久性及其抗肿瘤功能中的应用。最后,我们探讨了CRISPR/Cas9工程化CAR-T 细胞用于癌症治疗的临床试验。
As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy has been markedly improved in the past decade.
However, the clinical effect of CAR-T therapy is not so satisfying, especially in solid tumors. Even in hematologic malignancies, a proportion of patients eventually relapse after receiving CAR-T cell infusions, owing to the poor expansion and persistence of CAR-T cells. Recently, CRISPR/Cas9 technology has provided an effective approach to promoting the proliferation and persistence of CAR-T cells in the body.
This technology has been utilized in CAR-T cells to generate a memory phenotype, reduce exhaustion, and screen new targets to improve the anti-tumor potential. In this review, we aim to describe the major causes limiting the persistence of CAR-T cells in patients and discuss the application of CRISPR/Cas9 in promoting CAR-T cell persistence and its anti-tumor function.
Finally, we investigate clinical trials for CRISPR/Cas9-engineered CAR-T cells for the treatment of cancer.
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