自然杀伤细胞（NK细胞）是一种先天淋巴细胞，通过杀死病毒感染或肿瘤细胞，并分泌细胞因子和趋化因子，在免疫中发挥关键作用。由于其安全性和疗效，NK细胞介导的免疫疗法已成为治疗癌症的一种有前景的方法。NK细胞兴奋 (NKCEs) ，如双特异性杀伤细胞兴奋剂（BiKE）或三特异性杀伤细胞兴奋剂（TriKE），是一类新型的基于抗体的治疗药物，与利用NK细胞的其他癌症免疫疗法相比，具有几个优势。通过连接NK细胞和肿瘤细胞，NKCEs激活NK细胞并导致肿瘤细胞溶解。目前正在开发越来越多的NKCEs，其中一些已经进入临床试验。然而，需要进行更全面的研究来确定NKCEs的分子设计如何影响其功能和可制造性，这对于将其开发为用于癌症治疗的即开即用药物至关重要。在本综述中，我们总结了关于NKCE开发的当前知识，并讨论了生产有效NKCEs所需的关键因素。版权所有© 2023年张、林和徐。

Natural Killer (NK) cells are a type of innate lymphoid cells that play a crucial role in immunity by killing virally infected or tumor cells and secreting cytokines and chemokines. NK cell-mediated immunotherapy has emerged as a promising approach for cancer treatment due to its safety and effectiveness. NK cell engagers (NKCEs), such as BiKE (bispecific killer cell engager) or TriKE (trispecific killer cell engager), are a novel class of antibody-based therapeutics that exhibit several advantages over other cancer immunotherapies harnessing NK cells. By bridging NK and tumor cells, NKCEs activate NK cells and lead to tumor cell lysis. A growing number of NKCEs are currently undergoing development, with some already in clinical trials. However, there is a need for more comprehensive studies to determine how the molecular design of NKCEs affects their functionality and manufacturability, which are crucial for their development as off-the-shelf drugs for cancer treatment. In this review, we summarize current knowledge on NKCE development and discuss critical factors required for the production of effective NKCEs.Copyright © 2023 Zhang, Lam and Xu.