Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1
ABSTRACTAntibody-based immune checkpoint blockade (ICB)-based therapeutics have become effective clinical applications for cancers. Applications of monoclonal antibodies (mAbs) to de-activate the PD-1-PD-L1 pathway could effectively reverse the phenotype of depleted activated thymocytes (T cells) to...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2236740 |
| _version_ | 1797356254881906688 |
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| author | Mengzhen Jiang Man Liu Guodi Liu Jiawen Ma Lixin Zhang Shenlin Wang |
| author_facet | Mengzhen Jiang Man Liu Guodi Liu Jiawen Ma Lixin Zhang Shenlin Wang |
| author_sort | Mengzhen Jiang |
| collection | DOAJ |
| description | ABSTRACTAntibody-based immune checkpoint blockade (ICB)-based therapeutics have become effective clinical applications for cancers. Applications of monoclonal antibodies (mAbs) to de-activate the PD-1-PD-L1 pathway could effectively reverse the phenotype of depleted activated thymocytes (T cells) to recover their anti-tumoral activities. High-resolution structures of the complexes of the therapeutic monoclonal antibodies with PD-1 or PD-L1 have revealed the key inter-molecular interactions and provided valuable insights into the fundamental mechanisms by which these antibodies inhibit PD-L1-PD-1 binding. Each anti-PD-1 mAb exhibits a unique blockade mechanism, such as interference with large PD-1-PD-L1 contacting interfaces, steric hindrance by overlapping a small area of this site, or binding to an N-glycosylated site. In contrast, all therapeutic anti-PD-L1 mAbs bind to a similar area of PD-L1. Here, we summarized advances in the structural characterization of the complexes of commercial mAbs that target PD-1 or PD-L1. In particular, we focus on the unique characteristics of those mAb structures, epitopes, and blockade mechanisms. It is well known that the use of antibodies as anti-tumor drugs has increased recently and both PD-1 and PD-L1 have attracted substantial attention as target for antibodies derived from new technologies. By focusing on structural characterization, this review aims to aid the development of novel antibodies targeting PD-1 or PD-L1 in the future. |
| first_indexed | 2024-03-08T14:23:58Z |
| format | Article |
| id | doaj.art-2d2522248ef648fd90bc155223e64b00 |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-03-08T14:23:58Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-2d2522248ef648fd90bc155223e64b002024-01-13T11:27:51ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2236740Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1Mengzhen Jiang0Man Liu1Guodi Liu2Jiawen Ma3Lixin Zhang4Shenlin Wang5State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, ChinaABSTRACTAntibody-based immune checkpoint blockade (ICB)-based therapeutics have become effective clinical applications for cancers. Applications of monoclonal antibodies (mAbs) to de-activate the PD-1-PD-L1 pathway could effectively reverse the phenotype of depleted activated thymocytes (T cells) to recover their anti-tumoral activities. High-resolution structures of the complexes of the therapeutic monoclonal antibodies with PD-1 or PD-L1 have revealed the key inter-molecular interactions and provided valuable insights into the fundamental mechanisms by which these antibodies inhibit PD-L1-PD-1 binding. Each anti-PD-1 mAb exhibits a unique blockade mechanism, such as interference with large PD-1-PD-L1 contacting interfaces, steric hindrance by overlapping a small area of this site, or binding to an N-glycosylated site. In contrast, all therapeutic anti-PD-L1 mAbs bind to a similar area of PD-L1. Here, we summarized advances in the structural characterization of the complexes of commercial mAbs that target PD-1 or PD-L1. In particular, we focus on the unique characteristics of those mAb structures, epitopes, and blockade mechanisms. It is well known that the use of antibodies as anti-tumor drugs has increased recently and both PD-1 and PD-L1 have attracted substantial attention as target for antibodies derived from new technologies. By focusing on structural characterization, this review aims to aid the development of novel antibodies targeting PD-1 or PD-L1 in the future.https://www.tandfonline.com/doi/10.1080/19420862.2023.2236740Antibody structureantibody-antigen interactionsPD-1 |
| spellingShingle | Mengzhen Jiang Man Liu Guodi Liu Jiawen Ma Lixin Zhang Shenlin Wang Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 mAbs Antibody structure antibody-antigen interactions PD-1 |
| title | Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 |
| title_full | Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 |
| title_fullStr | Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 |
| title_full_unstemmed | Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 |
| title_short | Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1 |
| title_sort | advances in the structural characterization of complexes of therapeutic antibodies with pd 1 or pd l1 |
| topic | Antibody structure antibody-antigen interactions PD-1 |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2236740 |
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