A CD47 antibody with minimized erythrocyte and thrombocyte toxicities
文献类型：期刊论文
| 作者 | Pei, Min2,3,4; Dai, Xiao-Dong5; Jiang, Xiao-Fan1; Yuan, Cai-Yi1; Tan, Jie4; He, Kai-Feng1; Liu, Guo-Jian6; Zhu, Jin-Di5; Li, Huan-Huan4; Pan, Ai-Ling1 |
| 刊名 | FRONTIERS IN ONCOLOGY
 |
| 出版日期 | 2025-11-26 |
| 卷号 | 15页码:15 |
| 关键词 | CD47 monoclonal antibody macrophages hematotoxicity N-linked glycosylation |
| ISSN号 | 2234-943X |
| DOI | 10.3389/fonc.2025.1686180 |
| 通讯作者 | Wang, Chunhe(wangc@dartsbio.com) |
| 英文摘要 | Introduction Blockade of the CD47/SIRPa axis has emerged as a promising approach to enhance macrophage-mediated anti-tumor activities in cancer immunotherapy. However, the clinical application of early CD47 antibodies has been associated with significant hematotoxicities, including hemagglutination, anemia, and thrombopenia. Although several CD47 antibodies have generally avoided hemagglutination, anemia, and thrombopenia remain, potentially mediated by enhanced phagocytosis of erythrocytes and thrombocytes.Methods 1B2-10 is a humanized CD47-neutralizing antibody generated by mouse immunization and phage display technology. Its efficacy and safety were evaluated using in vitro assays, tumor xenograft models, and studies in cynomolgus monkeys. In silico modeling and mutagenesis analyses were performed to identify the 1B2-10 binding epitopes.Results In vitro, 1B2-10 exhibited minimized binding to erythrocytes and thrombocytes, did not induce hemagglutination, and reduced erythrocyte phagocytosis. It enhanced macrophage-mediated phagocytosis of tumor cells and showed potent antitumor effects as a monotherapy or in combination with a PD-1 antibody in tumor models. In cynomolgus monkeys, single doses of 1B2-10 at 120 mg/kg and repeated doses at 100 mg/kg were well-tolerated, with no significant hematological toxicities observed. In silico studies revealed the molecular basis for reduced erythrocyte binding, demonstrating that two critical N-linked glycans sterically masked epitopes.Discussion These findings suggest that 1B2-10 demonstrates a favorable efficacy and safety profile, indicating great therapeutic potential for cancer. Based on these studies, 1B2-10 has been renamed as DS003 and is currently advancing through Phase I clinical trials in China to further evaluate its safety profile and preliminary efficacy in human subjects. |
| WOS关键词 | ANTI-CD47 ANTIBODY ; LEMZOPARLIMAB ; BLOCKADE ; CANCER ; CELLS |
| 资助项目 | Guangdong ST Program[2022B1111070007] ; Zhongshan Innovation and Entrepreneurship Team project[CXTD2023007] ; National Natural Science Foundation of China[32370958] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:001634279000001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322351]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Chunhe |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 2.Jinan Univ, Inst Biomed, Coll Life Sci & Technol, Guangzhou, Peoples R China 3.Jinan Univ, Coll Life Sci & Technol, Dept Cell Biol, Guangzhou, Peoples R China 4.Shanghai Mabstone Biotechnol Ltd, Dept Antibody Discovery, Shanghai, Peoples R China 5.Chinese Acad Sci, Biotherapeut Discovery Res Ctr, Shanghai Inst Mat Med, Shanghai, Peoples R China 6.Dartsbio Pharmaceut Ltd, Dept Res & Dev Ctr, Zhongshan, Guangdong, Peoples R China 7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pei, Min,Dai, Xiao-Dong,Jiang, Xiao-Fan,et al. A CD47 antibody with minimized erythrocyte and thrombocyte toxicities[J]. FRONTIERS IN ONCOLOGY,2025,15:15. |
| APA | Pei, Min.,Dai, Xiao-Dong.,Jiang, Xiao-Fan.,Yuan, Cai-Yi.,Tan, Jie.,...&Wang, Chunhe.(2025).A CD47 antibody with minimized erythrocyte and thrombocyte toxicities.FRONTIERS IN ONCOLOGY,15,15. |
| MLA | Pei, Min,et al."A CD47 antibody with minimized erythrocyte and thrombocyte toxicities".FRONTIERS IN ONCOLOGY 15(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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