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针对恶性肿瘤中CD47/SIRPα信号通路的研究：最新进展、困难与未来展望

Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives.

作者信息

Jiang Chenyang, Sun Hao, Jiang Zhongxing, Tian Wenzhi, Cang Shundong, Yu Jifeng

机构信息

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People's Hospital, Henan University People's Hospital and Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Front Oncol. 2024 Jul 5;14:1378647. doi: 10.3389/fonc.2024.1378647. eCollection 2024.

DOI:10.3389/fonc.2024.1378647
PMID:39040441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11261161/
Abstract

Since its initial report in 2015, CD47 has garnered significant attention as an innate immune checkpoint, raising expectations to become the next "PD-1." The optimistic early stages of clinical development spurred a flurry of licensing deals for CD47-targeted molecules and company mergers or acquisitions for related assets. However, a series of setbacks unfolded recently, starting with the July 2023 announcement of discontinuing the phase 3 ENHANCE study on Magrolimab plus Azacitidine for higher-risk myelodysplastic syndromes (MDS). Subsequently, in August 2023, the termination of the ASPEN-02 program, assessing Evorpacept in combination with Azacitidine in MDS patients, was disclosed due to insufficient improvement compared to Azacitidine alone. These setbacks have cast doubt on the feasibility of targeting CD47 in the industry. In this review, we delve into the challenges of developing CD47-SIRPα-targeted drugs, analyze factors contributing to the mentioned setbacks, discuss future perspectives, and explore potential solutions for enhancing CD47-SIRPα-targeted drug development.

摘要

自2015年首次报道以来，CD47作为一种固有免疫检查点备受关注，人们期望它成为下一个“PD-1”。临床开发早期的乐观进展引发了一系列针对CD47靶向分子的授权交易以及相关资产的公司并购。然而，最近一系列挫折接踵而至，首先是2023年7月宣布停止针对高危骨髓增生异常综合征（MDS）的Magrolimab联合阿扎胞苷的3期ENHANCE研究。随后，2023年8月，评估Evorpacept联合阿扎胞苷治疗MDS患者的ASPEN-02项目因与单独使用阿扎胞苷相比改善不足而终止。这些挫折使业内对靶向CD47的可行性产生了怀疑。在本综述中，我们深入探讨开发CD47-SIRPα靶向药物的挑战，分析导致上述挫折的因素，讨论未来前景，并探索增强CD47-SIRPα靶向药物开发的潜在解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/6ff4d6e43cc6/fonc-14-1378647-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/47ece1b7a0dc/fonc-14-1378647-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/5736ae94aff3/fonc-14-1378647-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/6ff4d6e43cc6/fonc-14-1378647-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/47ece1b7a0dc/fonc-14-1378647-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/860329708046/fonc-14-1378647-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/5736ae94aff3/fonc-14-1378647-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/11261161/6ff4d6e43cc6/fonc-14-1378647-g004.jpg

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Nat Commun. 2024 Mar 6;15(1):2054. doi: 10.1038/s41467-024-46310-y.
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J Transl Med. 2024 Mar 1;22(1):220. doi: 10.1186/s12967-023-04710-6.
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Delivery of CD47-SIRPα checkpoint blocker by BCMA-directed UCAR-T cells enhances antitumor efficacy in multiple myeloma.
Ann Hematol. 2025 May 15. doi: 10.1007/s00277-025-06401-2.
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Emerging therapeutics targeting tumor-associated macrophages for the treatment of solid organ cancers.靶向肿瘤相关巨噬细胞治疗实体器官癌症的新兴疗法。
Expert Opin Emerg Drugs. 2025 Jun;30(2):109-147. doi: 10.1080/14728214.2025.2504376. Epub 2025 May 25.
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Antibodies (Basel). 2025 Mar 3;14(1):21. doi: 10.3390/antib14010021.
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