Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology
Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy<sup>®</s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/6/1190 |
| _version_ | 1818236307660341248 |
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| author | Hyun Tae Lee Sang Hyung Lee Yong-Seok Heo |
| author_facet | Hyun Tae Lee Sang Hyung Lee Yong-Seok Heo |
| author_sort | Hyun Tae Lee |
| collection | DOAJ |
| description | Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy<sup>®</sup>), nivolumab (Opdivo<sup>®</sup>), pembrolizumab (Keytruda<sup>®</sup>), cemiplimab (Libtayo<sup>®</sup>), atezolizumab (Tecentriq<sup>®</sup>), durvalumab (Imfinzi<sup>®</sup>), and avelumab (Bavencio<sup>®</sup>), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology. |
| first_indexed | 2024-12-12T12:07:47Z |
| format | Article |
| id | doaj.art-eb3f6cab4f914c65b9380350fcebf65a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T12:07:47Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-eb3f6cab4f914c65b9380350fcebf65a2022-12-22T00:24:58ZengMDPI AGMolecules1420-30492019-03-01246119010.3390/molecules24061190molecules24061190Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-OncologyHyun Tae Lee0Sang Hyung Lee1Yong-Seok Heo2Department of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaDepartment of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaDepartment of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy<sup>®</sup>), nivolumab (Opdivo<sup>®</sup>), pembrolizumab (Keytruda<sup>®</sup>), cemiplimab (Libtayo<sup>®</sup>), atezolizumab (Tecentriq<sup>®</sup>), durvalumab (Imfinzi<sup>®</sup>), and avelumab (Bavencio<sup>®</sup>), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology.https://www.mdpi.com/1420-3049/24/6/1190crystal structureimmune checkpointPD-1PD-L1CTLA-4cancertherapeutic antibody |
| spellingShingle | Hyun Tae Lee Sang Hyung Lee Yong-Seok Heo Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology Molecules crystal structure immune checkpoint PD-1 PD-L1 CTLA-4 cancer therapeutic antibody |
| title | Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology |
| title_full | Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology |
| title_fullStr | Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology |
| title_full_unstemmed | Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology |
| title_short | Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology |
| title_sort | molecular interactions of antibody drugs targeting pd 1 pd l1 and ctla 4 in immuno oncology |
| topic | crystal structure immune checkpoint PD-1 PD-L1 CTLA-4 cancer therapeutic antibody |
| url | https://www.mdpi.com/1420-3049/24/6/1190 |
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