Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China.
Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, China.
J Nanobiotechnology. 2020 Jan 13;18(1):12. doi: 10.1186/s12951-020-0571-2.
CD47, the integrin-related protein, plays an important role in immune resistance and escape of tumor cells. Antibodies blocking the CD47/SIRPα signal pathway can effectively stimulate macrophage-mediated phagocytosis of tumor cells, which becomes a promising approach for tumor immunotherapy. Nanobodies (Nbs) derived from camelid animals are emerging as a new force in antibody therapy.
HuNb1-IgG4, an innovative anti-CD47 nanobody, was developed with high affinity and specificity. It effectively enhanced macrophage-mediated phagocytosis of tumor cells in vitro and showed potent anti-ovarian and anti-lymphoma activity in vivo. Importantly, HuNb1-IgG4 did not induce the agglutination of human red blood cells (RBCs) in vitro and exhibited high safety for hematopoietic system in cynomolgus monkey. In addition, HuNb1-IgG4 could be produced on a large scale in CHO-S cells with high activity and good stability. Also, we established anti-CD47/CD20 bispecific antibody (BsAb) consisted of HuNb1 and Rituximab, showing more preference binding to tumor cells and more potent anti-lymphoma activity compared to HuNb1-IgG4.
Both of HuNb1-IgG4 and anti-CD47/CD20 BsAb are potent antagonists of CD47/SIRPα pathway and promising candidates for clinical trials.
CD47，整合素相关蛋白，在肿瘤细胞的免疫抵抗和逃逸中发挥重要作用。阻断 CD47/SIRPα信号通路的抗体可以有效刺激巨噬细胞介导的肿瘤细胞吞噬作用，这成为肿瘤免疫治疗的一种有前途的方法。来源于骆驼科动物的纳米抗体（Nbs）正在成为抗体治疗的新力量。
开发了具有高亲和力和特异性的新型抗 CD47 纳米抗体 HuNb1-IgG4。它能有效增强体外巨噬细胞介导的肿瘤细胞吞噬作用，并在体内显示出强大的抗卵巢癌和抗淋巴瘤活性。重要的是，HuNb1-IgG4 不会在体外引起人红细胞（RBC）的聚集，并且在食蟹猴的造血系统中具有很高的安全性。此外，HuNb1-IgG4 可以在 CHO-S 细胞中大规模生产，具有高活性和良好的稳定性。我们还建立了由 HuNb1 和利妥昔单抗组成的抗 CD47/CD20 双特异性抗体（BsAb），与 HuNb1-IgG4 相比，它对肿瘤细胞具有更强的结合偏好和更强的抗淋巴瘤活性。
HuNb1-IgG4 和抗 CD47/CD20 BsAb 均为 CD47/SIRPα 通路的有效拮抗剂，是临床试验的有前途的候选药物。
Zotero 插件
