School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Immunology Division, Pathology Department, University of Cambridge, Cambridge, UK.
Br J Haematol. 2021 Jun;193(5):946-950. doi: 10.1111/bjh.17496. Epub 2021 May 5.
Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 has recently been identified as a critical tumour checkpoint, augmenting the expression and function of programmed death-ligand 1. We raised a monoclonal antibody, A9E8, specific for Siglec-15 using phage display. A9E8 stained myeloid leukaemia cell lines and peripheral cluster of differentiation (CD)33 blasts and CD34 leukaemia stem cells from patients with acute myeloid leukaemia (AML). By contrast, there was minimal expression on healthy donor leucocytes or CD34 stem cells from non-AML donors, suggesting targeting Siglec-15 may have significant therapeutic advantages over its fellow Siglec CD33. After binding, A9E8 was rapidly internalised (half-life of 180 s) into K562 cells. Antibodies to Siglec-15 therefore hold therapeutic potential for AML treatment.
唾液酸结合免疫球蛋白样凝集素（Siglec）-15 最近被确定为一个关键的肿瘤检查点，增强了程序性死亡配体 1 的表达和功能。我们使用噬菌体展示技术，针对 Siglec-15 产生了一种单克隆抗体 A9E8。A9E8 染色髓系白血病细胞系和外周分化簇 (CD)33 原始细胞以及急性髓系白血病 (AML)患者的 CD34 白血病干细胞。相比之下，健康供体白细胞或非 AML 供体的 CD34 干细胞上的表达很少，这表明针对 Siglec-15 的治疗可能比其同类 Siglec CD33 具有显著的治疗优势。结合后，A9E8 迅速被内化（半衰期为 180s）进入 K562 细胞。因此，针对 Siglec-15 的抗体具有治疗 AML 的潜力。
