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IMM2520，一种用于癌症免疫治疗的新型抗CD47/PD-L1双特异性抗体。

IMM2520, a novel anti-CD47/PD-L1 bispecific antibody for cancer immune therapy.

作者信息

Yang Chunmei, Li Song, Chen Dianze, Liu Dandan, Yang Yanan, Guo Huiqin, Sun Nana, Bai Xing, Li Guanghui, Zhang Ruliang, Wang Tianxiang, Zhang Li, Peng Liang, Liu Sijin, Zhang Wei, Zhao Gui, Tu Xiaoping, Tian Wenzhi

机构信息

Department of R&D, ImmuneOnco Biopharmaceuticals (Shanghai) Inc., Shanghai, 201203, China.

Department of CMC, ImmuneOnco Biopharmaceuticals (Shanghai) Inc., Shanghai, 201203, China.

出版信息

Heliyon. 2024 Oct 26;10(21):e39858. doi: 10.1016/j.heliyon.2024.e39858. eCollection 2024 Nov 15.

DOI:10.1016/j.heliyon.2024.e39858
PMID:39553551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11564011/
Abstract

PD-1/PD-L1 is an important signaling pathway in the adaptive immune system. The CD47/SIRPα signaling pathway is a crucial "do not eat me" signal for innate immunity. This study evaluated the anti-tumor mechanism of IMM2520 and . IMM2520 was generated using the "mab-trap" platform. IMM2520 showed high affinity to PD-L1 and relatively lower affinity to CD47, displaying preferential binding to PD-L1 on tumor cells. IMM2520 had the potent ability to inhibit the PD-1/PD-L1 and CD47/SIRPα signaling pathways and killed tumor cells through ADCC and ADCP. Importantly, IMM2520 did not bind to human red blood cells or induce erythrocyte agglutination. IMM2520 demonstrated a tendency to bind to CD47/PD-L1 tumor cells, reducing its binding to CD47 single-positive cells. In mouse transplantation models, compared with the first-generation CD47/PD-L1 BsAb (IMM2505), IMM2520 exhibited stronger and dose-dependent antitumor activity. These findings imply that IMM2520 may offer a novel therapeutic alternative for cancer patients.

摘要

PD-1/PD-L1是适应性免疫系统中的一条重要信号通路。CD47/SIRPα信号通路是先天性免疫的关键“别吃我”信号。本研究评估了IMM2520的抗肿瘤机制。IMM2520是使用“单抗捕获”平台生成的。IMM2520对PD-L1表现出高亲和力，对CD47的亲和力相对较低，显示出对肿瘤细胞上PD-L1的优先结合。IMM2520具有抑制PD-1/PD-L1和CD47/SIRPα信号通路的强大能力，并通过抗体依赖的细胞介导的细胞毒性作用（ADCC）和抗体依赖的细胞吞噬作用（ADCP）杀死肿瘤细胞。重要的是，IMM2520不与人红细胞结合或诱导红细胞凝集。IMM2520表现出与CD47/PD-L1肿瘤细胞结合的倾向，减少了其与CD47单阳性细胞的结合。在小鼠移植模型中，与第一代CD47/PD-L1双特异性抗体（IMM2505）相比，IMM2520表现出更强的剂量依赖性抗肿瘤活性。这些发现表明IMM2520可能为癌症患者提供一种新的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/83cb9a5f9613/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/cc1249961bc4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/ea0e589ff145/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/d68f287c5853/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/b3168ad40ecd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/af64bda3a9e6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/38316e4090c6/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/13926fabc57f/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/83cb9a5f9613/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/cc1249961bc4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/ea0e589ff145/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/d68f287c5853/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/b3168ad40ecd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/af64bda3a9e6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/38316e4090c6/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/13926fabc57f/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c5b/11564011/83cb9a5f9613/gr8.jpg

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本文引用的文献

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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据：全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models.
HX009，一种新型的双抗 PD1xCD47，在临床前模型中显示出强大的抗淋巴瘤活性。
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Blockade of dual immune checkpoint inhibitory signals with a CD47/PD-L1 bispecific antibody for cancer treatment.阻断 CD47/PD-L1 双免疫检查点抑制信号的抗体在癌症治疗中的应用。
Theranostics. 2023 Jan 1;13(1):148-160. doi: 10.7150/thno.79367. eCollection 2023.
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SIRPα-Fc fusion protein IMM01 exhibits dual anti-tumor activities by targeting CD47/SIRPα signal pathway via blocking the "don't eat me" signal and activating the "eat me" signal.SIRPα-Fc 融合蛋白 IMM01 通过阻断“别吃我”信号并激活“吃我”信号，靶向 CD47/SIRPα 信号通路，发挥双重抗肿瘤活性。
J Hematol Oncol. 2022 Nov 16;15(1):167. doi: 10.1186/s13045-022-01385-2.
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Crystal Structure of Human CD47 in Complex with Engineered SIRPα.D1(N80A).人 CD47 与工程化 SIRPα.D1(N80A)复合物的晶体结构。
Molecules. 2022 Aug 30;27(17):5574. doi: 10.3390/molecules27175574.
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Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes.抗 CD47 单克隆抗体 CC-90002 治疗复发/难治性急性髓系白血病和高危骨髓增生异常综合征患者的 1 期研究。
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