Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody
文献类型：期刊论文
| 作者 | Wang, Yongmei4,5; Chen, Yi-Li2,3; Xu, Hui4,5; Rana, Gul E.4,5; Tan, Xiaorong5; He, Mengying5; Jing, Qingqing1; Wang, Qi5; Wang, Guifeng4,5 ; Xie, Zuoquan4,5
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| 刊名 | FRONTIERS IN IMMUNOLOGY
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| 出版日期 | 2024-07-15 |
| 卷号 | 15页码:16 |
| 关键词 | antibody humanization programmed death-1 FR shuffling CDR grafting immunogenicity |
| ISSN号 | 1664-3224 |
| DOI | 10.3389/fimmu.2024.1395854 |
| 通讯作者 | Wang, Guifeng(gfwang@simm.ac.cn) ; Xie, Zuoquan(zqxie@simm.ac.cn) ; Wang, Chunhe(wangc@simm.ac.cn) |
| 英文摘要 | Introduction Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans.Methods Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies.Results While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background.Discussion The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field. |
| WOS关键词 | RESHAPING HUMAN-ANTIBODIES ; IMMUNOGENICITY ; PREDICTION ; VALIDATION ; DESIGN |
| 资助项目 | Key-Area Research and Development Program of Guangdong Province[2022B1111070007] ; National Natural Science Foundation of China[81872785] ; National Natural Science Foundation of China[32370958] ; Shanghai Municipal Commission of Science and Technology of China[21S11904500] ; Major Scientific and Technological Special Project of Zhongshan City[210205143867019] ; CAS Bohai Rim Advanced Research Institute for Drug Discovery Project[LX211005] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:001278074500001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312550]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Guifeng; Xie, Zuoquan; Wang, Chunhe |
| 作者单位 | 1.Shanghai Genechem Co Ltd, Antibody Dev Dept, Shanghai, Peoples R China 2.Shanghai Mabstone Biotechnol Ltd, Shanghai, Peoples R China 3.Dartsbio Pharmaceut Ltd, Zhongshan, Guangdong, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yongmei,Chen, Yi-Li,Xu, Hui,et al. Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody[J]. FRONTIERS IN IMMUNOLOGY,2024,15:16. |
| APA | Wang, Yongmei.,Chen, Yi-Li.,Xu, Hui.,Rana, Gul E..,Tan, Xiaorong.,...&Wang, Chunhe.(2024).Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody.FRONTIERS IN IMMUNOLOGY,15,16. |
| MLA | Wang, Yongmei,et al."Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody".FRONTIERS IN IMMUNOLOGY 15(2024):16. |
入库方式： OAI收割
来源：上海药物研究所
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