Glycostem Therapeutics, Kloosterstraat 9, 5349 AB, Oss, The Netherlands.
J Hematol Oncol. 2022 Nov 8;15(1):164. doi: 10.1186/s13045-022-01382-5.
Natural killer (NK) cells are unique immune effectors able to kill cancer cells by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for cancer and has recently emerged with hundreds of clinical trials paving the way to finally achieve market authorization. Advantages of NK cell therapies include the use of allogenic cell sources, off-the-shelf availability, and no risk of graft-versus-host disease (GvHD). Allogeneic NK cell therapies have reached the clinical stage as ex vivo expanded and differentiated non-engineered cells, as chimeric antigen receptor (CAR)-engineered or CD16-engineered products, or as combination therapies with antibodies, priming agents, and other drugs. This review summarizes the recent clinical status of allogeneic NK cell-based therapies for the treatment of hematological and solid tumors, discussing the main characteristics of the different cell sources used for NK product development, their use in cell manufacturing processes, the engineering methods and strategies adopted for genetically modified products, and the chosen approaches for combination therapies. A comparative analysis between NK-based non-engineered, engineered, and combination therapies is presented, examining the choices made by product developers regarding the NK cell source and the targeted tumor indications, for both solid and hematological cancers. Clinical trial outcomes are discussed and, when available, assessed in comparison with preclinical data. Regulatory challenges for product approval are reviewed, highlighting the lack of specificity of requirements and standardization between products. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.
自然杀伤 (NK) 细胞是独特的免疫效应细胞,能够通过直接识别表面配体杀死癌细胞,而无需预先致敏。同种异体 NK 细胞转移是一种非常有价值的癌症治疗选择,最近已有数百项临床试验为最终实现市场授权铺平了道路。NK 细胞疗法的优势包括使用同种异体细胞来源、现成可用性和无移植物抗宿主病 (GvHD) 风险。同种异体 NK 细胞疗法已经进入临床阶段,作为体外扩增和分化的非工程细胞、嵌合抗原受体 (CAR) 工程或 CD16 工程产品,或作为与抗体、启动剂和其他药物的联合疗法。本综述总结了同种异体 NK 细胞为基础的治疗血液系统和实体肿瘤的最新临床现状,讨论了用于 NK 产品开发的不同细胞来源的主要特征,其在细胞制造过程中的用途,用于基因修饰产品的工程方法和策略,以及联合疗法的选择方法。对基于 NK 的非工程、工程和联合疗法进行了比较分析,检查了产品开发人员在 NK 细胞来源和靶向肿瘤适应症方面的选择,包括血液系统和实体瘤癌症。讨论了临床试验结果,并在可用时与临床前数据进行了比较。审查了产品批准的监管挑战,强调了产品之间要求和标准化的缺乏特异性。此外,还介绍了竞争格局和商业领域。本综述全面概述了生物技术和制药公司以及学术中心为将 NK 细胞疗法推向关键临床试验阶段和市场授权所做的努力。
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