一种新型Siglec-15抗体通过改造其fc介导的效应功能来增强其抗肿瘤效力。

IF 3.2 4区 医学 Q3 IMMUNOLOGY Journal of Immunotherapy Pub Date : 2023-06-01 DOI:10.1097/CJI.0000000000000465
Huandi Ding, Bing Yao, Lei Ci, Jing Feng, Pingkai Ouyang, Guoguang Chen, Xiwu Hui, Demin Zhou
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引用次数: 0

摘要

siglece -15是一种抑制免疫检查点,是癌症免疫治疗的新兴靶点。阻断siglece -15的功能是癌症治疗的一种极好的策略,抗体阻断已被用于靶向siglece -15。然而,fc介导的效应物功能是否有助于抗体的治疗效果尚不清楚。在此,我们制备了一种单克隆抗体1-15D1,该抗体与siglece -15具有高结合亲和力,并在体外强烈激活t细胞免疫反应。随后,我们在siglece -15人源化小鼠模型中探索了fc介导的1-15D1效应物功能,并在小鼠IgG2a同型组中观察到其抗肿瘤功效的进一步提高。因此,我们证明了1-15D1的抗肿瘤作用是通过多种因素介导的。除了t细胞免疫应答外,研究人员还探索了2种新的机制,包括细胞表面siglece -15的内化和fc介导的效应功能。综上所述,我们的研究不仅为改善癌症免疫治疗提供了一种潜在的药物,而且表明fc介导的免疫调节的特定作用可能提高siglece -15单克隆抗体的治疗效力。
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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Enhancing the Anti-tumor Potency of a Novel Siglec-15 Antibody by Engineering its Fc-mediated Effector Functions.

Siglec-15, an inhibitory immune checkpoint, is an emerging target in cancer immunotherapy. Blocking the function of Siglec-15 is an excellent strategy for cancer treatment and antibody blockade has been used to target Siglec-15. However, whether Fc-mediated effector functions contribute to the therapeutic effect of antibodies remains unclear. Herein, we generated a monoclonal antibody, 1-15D1, which had a high binding affinity with Siglec-15 and strongly activated T-cell immune response in vitro. Subsequently, the Fc-mediated effector functions of 1-15D1 were explored in a Siglec-15 humanized mouse model, and further improvement in antitumor efficacy was observed in the mouse IgG2a isotype group. Thus, we demonstrate that the antitumor effects of 1-15D1 were mediated via multiple factors. In addition to the T-cell immune response, 2 novel mechanisms were explored, including the internalization of the cell surface Siglec-15 and Fc-mediated effector functions. In conclusion, our studies not only provide a potential agent for the improvement of cancer immunotherapy but also suggest that a specific role of Fc-mediated immune regulation may improve the therapeutic potency of Siglec-15 monoclonal antibody.

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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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