Investigating the structure:function relationships of a novel human myeloid checkpoint receptor (LILRB3) and its specific immunomodulating monoclonal

研究新型人骨髓检查点受体（LILRB3）及其特异性免疫调节单克隆抗体的结构：功能关系

• 批准号: 2882002
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2882002
• 关键词: Investigating; structure; function; relationships; novel

We aim to investigate the consequences of the ectopic expression of LILRB3 on solid tumour cells and will test the impact of LILRB3 in three parallel settings, where it is either expressed on myeloid cells, tumour cells or both compartments. Furthermore, we will investigate whether LILRB3 blocking/antagonistic mAbs can treat established tumours. The structural analysis of the LILRB3-mAb complexes will reveal the binding modes of different mAbs and will provide molecular insight into the mechanisms underpinning the regulation of LILRB3.A partial crystal structure of LILRB3-bound with mAb has been determined (Figure 2). As there are no welldefined ligands for LILRB3, our mAbs, along with pre-clinical modes, provide ideal tools to study the keyconserved epitopes and functional consequences of LILRB3 ligation on myeloid and tumour cells.

我们的目标是研究LILRB3异位表达对实体肿瘤细胞的影响，并将在三种平行环境中测试LILRB3的影响，其中LILRB3在骨髓细胞、肿瘤细胞或两种细胞室中表达。此外，我们将研究LILRB3阻断/拮抗单克隆抗体是否可以治疗已建立的肿瘤。LILRB3- mab复合物的结构分析将揭示不同mab的结合模式，并为LILRB3的调控机制提供分子视角。已经确定了与单抗结合的lilrb3的部分晶体结构（图2）。由于没有明确定义的LILRB3配体，我们的单克隆抗体以及临床前模型，为研究LILRB3连接对髓细胞和肿瘤细胞的键保守表位和功能后果提供了理想的工具。