IMM47是一种靶向CD24的人源化单克隆抗体,通过阻断CD24/Siglec-10相互作用表现出非凡的抗肿瘤功效,可作为单一疗法或与抗PD1抗体联合用于癌症免疫疗法。

Q2 Medicine Antibody Therapeutics Pub Date : 2023-09-09 eCollection Date: 2023-10-01 DOI:10.1093/abt/tbad020
Song Li, Dianze Chen, Huiqin Guo, Yanan Yang, Dandan Liu, Chunmei Yang, Xing Bai, Wei Zhang, Li Zhang, Gui Zhao, Xiaoping Tu, Liang Peng, Sijin Liu, Yongping Song, Zhongxing Jiang, Ruliang Zhang, Jifeng Yu, Wenzhi Tian
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引用次数: 0

摘要

本研究评估了人源化抗CD24单克隆抗体IMM47的抗肿瘤机制。生物层干涉法、ELISA和流式细胞术方法用于测量IMM47的结合、亲和力、ADCC、ADCP、ADCT和CDC活性。在移植小鼠模型中测量体内治疗效果。IMM47显著结合粒细胞但不结合人红细胞,并阻断CD24结合Siglec-10的能力。IMM47对REH细胞具有较强的ADCC、ADCT和ADCP活性。IMM47的体内药效学表明,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。IMM47与Tislelizumab、Opdivo和Keytruda联合使用时,也具有强大的协同治疗功效,通过巨噬细胞抗原呈递阻断CD24/Siglec-10相互作用,具有强大的ADCC、ADCP、ADCT和CDC活性,并且具有安全性。IMM47与CD24的结合独立于细胞外结构域的N-糖基化修饰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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IMM47, a humanized monoclonal antibody that targets CD24, exhibits exceptional anti-tumor efficacy by blocking the CD24/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy.

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. In vivo 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 in vivo 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.

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来源期刊
Antibody Therapeutics
Antibody Therapeutics Medicine-Immunology and Allergy
CiteScore
8.70
自引率
0.00%
发文量
30
审稿时长
8 weeks
期刊最新文献
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