Azevedo Júlia Teixeira Cottas de, Godoy Juliana Aparecida Preto de, Souza Cláudia de, Sielski Micheli Severo, Coa Larissa Leggieri, Barbosa Júnior Augusto, Kerbauy Lucila Nassif, Kondo Andrea Tiemi, Okamoto Oswaldo Keith, Hamerschlak Nelson, Kutner José Mauro, Paiva Raquel de Melo Alves
Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
Einstein (Sao Paulo). 2024 Dec 9;22:eRW0612. doi: 10.31744/einstein_journal/2024RW0612. eCollection 2024.
Natural Killer cells are immune leukocytes required for responses against tumor cells and virus-infected cells. In the last decade, natural killer cells have emerged as promising tools in cancer therapy, and clinical studies on patients treated with natural killer cells have revealed increased rates of disease-free survival. In this article, we review results from the major clinical trials that have used natural killer cells for cancer treatment, including their global distribution. We also discuss the major mechanisms of natural killer cell activation and expansion and focus on the advantages and disadvantages of each mechanism for clinical applications. Although natural killer cells can be isolated from several sources, primary natural killer cells are most commonly used in clinical trials. However, the frequency of natural killer cells available in peripheral and cord blood is low, necessitating development of methods for expansion of natural killer cells for clinical use. The development of a platform for the expansion of large-scale good manufacturing practice-compliant natural killer cells has limitations as several methods for natural killer cell activation and expansion yield conflicting results. Only techniques using feeder cells can produce large numbers of cells, allowing the "off-the-shelf" use of natural killer cells. However, advances in cell culture have supported the development of feeder-free platforms for natural killer cell expansion, which is fundamental for improving the safety of this type of cell therapy.
自然杀伤细胞是对抗肿瘤细胞和病毒感染细胞的免疫白细胞。在过去十年中，自然杀伤细胞已成为癌症治疗中有前景的工具，对接受自然杀伤细胞治疗的患者的临床研究显示无病生存率有所提高。在本文中，我们回顾了使用自然杀伤细胞进行癌症治疗的主要临床试验结果，包括其全球分布情况。我们还讨论了自然杀伤细胞激活和扩增的主要机制，并重点关注每种机制在临床应用中的优缺点。虽然自然杀伤细胞可以从多种来源分离，但原代自然杀伤细胞在临床试验中最常用。然而，外周血和脐带血中可获得的自然杀伤细胞频率较低，因此需要开发用于临床使用的自然杀伤细胞扩增方法。用于大规模符合药品生产质量管理规范的自然杀伤细胞扩增的平台开发存在局限性，因为几种自然杀伤细胞激活和扩增方法产生的结果相互矛盾。只有使用饲养细胞的技术才能产生大量细胞，从而实现自然杀伤细胞的“现货”使用。然而，细胞培养技术的进步支持了用于自然杀伤细胞扩增的无饲养细胞平台的开发，这对于提高这种细胞疗法的安全性至关重要。
