Neural cell adhesion molecule 1 (NCAM1/CD56) is expressed on immune cells, myoblasts, and malignant cells, and there is a growing demand for the genetic detection of CD56 and CD56-targeted therapy. In the present study, we developed a novel peptide ligand (designated Natein) that binds to human CD56 by using T7 phage display technology. Natein recognized the extracellular region of CD56 and could bind to natural killer (NK) cells and CD56-positive (CD56⁺) cancer cells. CD56⁺ cells enriched from human peripheral blood mononuclear cells (PBMCs) using biotinylated Natein-conjugated microbeads, similarly to CD56 antibody-isolated cells, demonstrated functional cytotoxicity against K562 cells. In addition, Natein could be used to stain CD56⁺ lymphoma cells in nasal-type extranodal NK/T-cell lymphoma tissues similarly to a CD56 antibody. These findings suggest that Natein has the potential to be alternative to CD56 antibody that could be used for peptide-based cell isolation and diagnosis.

神经细胞粘附分子 1 (NCAM1/CD56) 在免疫细胞、成肌细胞和恶性细胞上表达，对 CD56 和 CD56 靶向治疗的基因检测的需求不断增长。在本研究中，我们开发了一种新型肽配体（命名为 Natein），通过使用 T7 噬菌体展示技术与人类 CD56 结合。Natein 识别 CD56 的细胞外区域，可以与自然杀伤 (NK) 细胞和 CD56 阳性 (CD56 ⁺ ) 癌细胞结合。与 CD56 抗体分离的细胞类似，使用生物素化 Natein 偶联微珠从人外周血单核细胞 (PBMC) 中富集的CD56 ⁺细胞显示出对 K562 细胞的功能性细胞毒性。此外，Natein 可用于染色 CD56 ⁺鼻型结外 NK/T 细胞淋巴瘤组织中的淋巴瘤细胞类似于 CD56 抗体。这些发现表明 Natein 有可能替代 CD56 抗体，可用于基于肽的细胞分离和诊断。