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Abstract：
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.
摘要：
基因工程的最新进展使修饰自然杀伤（NK）细胞成为可能，以增强其对抗各种癌症的能力。包括实体瘤.本综述讨论了基因工程嵌合抗原受体NK细胞疗法的现状及其治疗实体瘤的潜力。我们探讨NK细胞的固有特性及其在免疫调节和肿瘤监测中的作用。此外，我们研究了用于基因改造NK细胞的策略，安全概况,和潜在的临床应用。我们的研究表明，CAR-NK细胞可以有效地靶向和消退非血液恶性肿瘤，显示增强的抗肿瘤功效。这意味着使用遗传修饰的NK细胞治疗肿瘤的极好前景。值得注意的是,NK细胞表现出低的移植物抗宿主病（GvHD）潜力，很少诱导显著的毒性，使它们成为汽车工程的理想平台。同种异体NK细胞过继转移到患者中进一步强调了NK细胞用于各种应用的多功能性。我们还解决了与基因工程NK细胞疗法的临床翻译相关的挑战和局限性，比如脱靶效应，免疫逃逸机制，和制造可扩展性。我们提供了通过组合疗法和递送优化来克服这些障碍的策略。总的来说,我们相信这篇综述通过阐明潜在的机制，有助于推进NK细胞免疫疗法作为一种有前途的癌症治疗方法，评估临床前和临床证据，解决剩余的挑战。
