Choi Hyeree, Ho Michelle, Adeniji Opeyemi S, Giron Leila, Bordoloi Devivasha, Kulkarni Abhijeet J, Puchalt Alfredo Perales, Abdel-Mohsen Mohamed, Muthumani Kar
Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
Front Oncol. 2021 Nov 19;11:778989. doi: 10.3389/fonc.2021.778989. eCollection 2021.
Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.
唾液酸结合免疫球蛋白样凝集素9（Siglec-9）是一种在多种免疫细胞上表达的糖免疫负性检查点。Siglec-9通过与癌细胞上表达的唾液酸聚糖配体结合发挥其抑制作用，使癌细胞能够逃避免疫监视。我们通过用编码Siglec-9的DNA和Siglec-9蛋白免疫小鼠，开发了一组人抗Siglec-9杂交瘤克隆。通过克隆筛选鉴定出了对Siglec-9具有高特异性和功能的先导抗体。细胞毒性试验表明，我们的先导抗体增强了抗肿瘤免疫活性。此外，利用卵巢癌人源化小鼠模型进行的测试显示肿瘤体积大幅减小。总之，我们开发了新型抗体，通过干扰Siglec-9介导的免疫抑制来增强抗肿瘤免疫力。
