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:Antitumor activity of genetically engineered NK-cells in non-hematological solid tumor: a comprehensive review.
Antitumor activity of genetically engineered NK-cells in non-hematological solid tumor: a comprehensive review.
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基因工程的最新进展使人们能够改造自然杀伤(NK)细胞,增强其对抗多种癌症(包括实体瘤)的能力。本综述全面介绍基因工程嵌合抗原受体 NK(CAR-NK)细胞疗法的现状及其治疗实体瘤的潜力。文章讨论 NK 细胞的固有特性及其在免疫调节和肿瘤监视中的作用,并从疗效、安全性和潜在临床应用角度审视 NK 细胞基因工程策略。研究表明,CAR-NK 可有效靶向并使非血液系统恶性肿瘤消退,显示出增强的抗肿瘤疗效,提示基因改造 NK 细胞治疗肿瘤前景广阔。
值得注意的是,NK 细胞发生移植物抗宿主病(GvHD)的可能性低,也很少诱发严重毒性,因此是理想的 CAR 工程平台。将异基因 NK 细胞过继转移至患者体内,也进一步体现了 NK 细胞应用的多样性。文章还讨论基因工程 NK 细胞疗法临床转化面临的挑战和局限,如脱靶效应、免疫逃逸机制及规模化生产,并提出通过联合治疗和优化递送克服这些障碍的策略。
总体而言,本综述阐明潜在机制、评估临床前和临床证据并讨论未解决挑战,有助于推进 NK 细胞免疫疗法成为有前景的癌症治疗方法。
Recent advancements in genetic engineering have made it possible to modify Natural Killer (NK) cells to enhance their ability to fight against various cancers, including solid tumors. This comprehensive overview discusses the current status of genetically engineered chimeric antigen receptor NK-cell therapies and their potential for treating solid tumors.
We explore the inherent characteristics of NK cells and their role in immune regulation and tumor surveillance.
Moreover, we examine the strategies used to genetically engineer NK cells in terms of efficacy, safety profile, and potential clinical applications.
Our investigation suggests CAR-NK cells can effectively target and regress non-hematological malignancies, demonstrating enhanced antitumor efficacy. This implies excellent promise for treating tumors using genetically modified NK cells.
Notably, NK cells exhibit low graft versus host disease (GvHD) potential and rarely induce significant toxicities, making them an ideal platform for CAR engineering. The adoptive transfer of allogeneic NK cells into patients further emphasizes the versatility of NK cells for various applications.
We also address challenges and limitations associated with the clinical translation of genetically engineered NK-cell therapies, such as off-target effects, immune escape mechanisms, and manufacturing scalability.
We provide strategies to overcome these obstacles through combination therapies and delivery optimization.
Overall, we believe this review contributes to advancing NK-cell-based immunotherapy as a promising approach for cancer treatment by elucidating the underlying mechanisms, evaluating preclinical and clinical evidence, and addressing remaining challenges.
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