Li Song, Chen Dianze, Guo Huiqin, Yang Yanan, Liu Dandan, Yang Chunmei, Bai Xing, Zhang Wei, Zhang Li, Zhao Gui, Tu Xiaoping, Peng Liang, Liu Sijin, Song Yongping, Jiang Zhongxing, Zhang Ruliang, Yu Jifeng, Tian Wenzhi
ImmuneOnco Biopharmaceuticals (Shanghai) Inc., Shanghai 201203, China.
Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450051, China.
Antib Ther. 2023 Sep 9;6(4):240-252. doi: 10.1093/abt/tbad020. eCollection 2023 Oct.
This study evaluates the anti-tumor mechanism of IMM47, a humanized anti-CD24 mAb. Biolayer interferometry, ELISA and flow cytometry methods were used to measure the IMM47 binding, affinity, ADCC, ADCP, ADCT and CDC activities. therapeutical efficacy was measured in transplanted mouse models. IMM47 significantly binds granulocytes but not human erythrocytes and blocks CD24's ability to bind to Siglec-10. IMM47 has strong ADCC, ADCT and ADCP activity against REH cells. IMM47's pharmacodynamics showed that IMM47 has strong anti-tumor effects in human siglec-10 transgenic mouse models with a memory immune response. IMM47 also has powerful synergistic therapeutic efficacy when combined with Tislelizumab, Opdivo and Keytruda, by blocking CD24/Siglec-10 interaction through macrophage antigen presentation with strong ADCC, ADCP, ADCT and CDC activities and with a safe profile. IMM47 binding to CD24 is independent of N-glycosylation modification of the extracellular domain.
本研究评估了人源化抗CD24单克隆抗体IMM47的抗肿瘤机制。采用生物膜干涉技术、酶联免疫吸附测定法和流式细胞术来检测IMM47的结合、亲和力、抗体依赖的细胞介导的细胞毒性（ADCC）、抗体依赖的细胞吞噬作用（ADCP）、抗体依赖的细胞介导的细胞毒性（ADCT）和补体依赖的细胞毒性（CDC）活性。在移植小鼠模型中测定治疗效果。IMM47能显著结合粒细胞，但不与人红细胞结合，并阻断CD24与Siglec-10结合的能力。IMM47对REH细胞具有较强的ADCC、ADCT和ADCP活性。IMM47的药效学表明，IMM47在具有记忆免疫反应的人Siglec-10转基因小鼠模型中具有较强的抗肿瘤作用。当与替雷利珠单抗、纳武利尤单抗和帕博利珠单抗联合使用时，IMM47还具有强大的协同治疗效果，通过巨噬细胞抗原呈递阻断CD24/Siglec-10相互作用，具有较强的ADCC、ADCP、ADCT和CDC活性，且安全性良好。IMM47与CD24的结合不依赖于细胞外结构域的N-糖基化修饰。
