Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Beijing Institute of Biotechnology, Beijing, China.
Biochem Biophys Res Commun. 2021 Jan 1;534:134-140. doi: 10.1016/j.bbrc.2020.12.013. Epub 2020 Dec 16.
TIGIT is an emerging novel checkpoint target that is expressed on both tumor-infiltrating T cells and NK cells. Some current investigational antibodies targeting TIGIT have also achieved dramatic antitumor efficacy in late clinical research. Most recently, the relevance of NK cell-associated TIGIT signaling pathway to tumors' evasion of the immune system has been clearly revealed, which endows NK cells with a pivotal role in the therapeutic effects of TIGIT blockade. In this article, we describe a novel anti-TIGIT monoclonal antibody, AET2010, which was acquired from a phage-displayed human single-chain antibody library through a cell panning strategy. With emphasis on its regulation of NK cells, we confirmed the excellent ex vivo and in vivo antitumor immunity of AET2010 mediated by the NK-92MI cells. Intriguingly, our work also revealed that AET2010 displays a lower affinity but parallel avidity and activity relative to MK7684, an investigational monoclonal antibody from MSD, implying a reasonable balance of potency and potential side effects for AET2010. Together, these results are promising and warrant further development of AET2010.
TIGIT 是一种新兴的新型检查点靶点，表达于肿瘤浸润 T 细胞和 NK 细胞上。一些目前正在研究的针对 TIGIT 的抗体在后期临床研究中也取得了显著的抗肿瘤疗效。最近，NK 细胞相关的 TIGIT 信号通路与肿瘤逃避免疫系统的相关性已被清楚揭示，这赋予了 NK 细胞在 TIGIT 阻断治疗效果中的关键作用。在本文中，我们描述了一种新型抗 TIGIT 单克隆抗体 AET2010，它是通过细胞淘选策略从噬菌体展示的人源单链抗体文库中获得的。我们特别强调了其对 NK 细胞的调节作用，证实了 AET2010 通过 NK-92MI 细胞介导的优异的体外和体内抗肿瘤免疫活性。有趣的是，我们的工作还揭示了 AET2010 与 MSD 的研究性单克隆抗体 MK7684 相比，显示出较低的亲和力，但平行的亲和力和活性，这意味着 AET2010 具有合理的效力和潜在副作用之间的平衡。总之，这些结果很有前景，值得进一步开发 AET2010。
