Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB
BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immunosurveillance. Immunotherapies involving ICs either block or stimulate these pathways and enhance the efficiency of the immune system to recognize and attack cancer cells. In this way, the development of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1129323/full |
| _version_ | 1797833165524434944 |
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| author | Taciana Manso Anjana Kushwaha Nika Abdollahi Patrice Duroux Véronique Giudicelli Sofia Kossida |
| author_facet | Taciana Manso Anjana Kushwaha Nika Abdollahi Patrice Duroux Véronique Giudicelli Sofia Kossida |
| author_sort | Taciana Manso |
| collection | DOAJ |
| description | BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immunosurveillance. Immunotherapies involving ICs either block or stimulate these pathways and enhance the efficiency of the immune system to recognize and attack cancer cells. In this way, the development of monoclonal antibodies (mAbs) targeting ICs has significant success in cancer treatment. Recently, a systematic description of the mechanisms of action (MOA) of the mAbs has been introduced in IMGT/mAb-DB, the IMGT® database dedicated to mAbs for therapeutic applications. The characterization of these antibodies provides a comprehensive understanding of how mAbs work in cancer.MethodsIn depth biocuration taking advantage of the abundant literature data as well as amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, allowed to define a standardized and consistent description of the MOA of mAbs targeting immune checkpoints in cancer therapy.ResultsA fine description and a standardized graphical representation of the MOA of selected mAbs are integrated within IMGT/mAb-DB highlighting two main mechanisms in cancer immunotherapy, either Blocking or Agonist. In both cases, the mAbs enhance cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune response (Immunostimulant effect) against tumor cells. On the one hand, mAbs targeting co-inhibitory receptors may have a functional Fc region to increase anti-tumor activity by effector properties that deplete Treg cells (Fc-effector function effect) or may have limited FcγR binding to prevent Teff cells depletion and reduce adverse events. On the other hand, agonist mAbs targeting co-stimulatory receptors may bind to FcγRs, resulting in antibody crosslinking (FcγR crosslinking effect) and substantial agonism.ConclusionIn IMGT/mAb-DB, mAbs for cancer therapy are characterized by their chains, domains and sequence and by several therapeutic metadata, including their MOA. MOAs were recently included as a search criterion to query the database. IMGT® is continuing standardized work to describe the MOA of mAbs targeting additional immune checkpoints and novel molecules in cancer therapy, as well as expanding this study to other clinical domains. |
| first_indexed | 2024-04-09T14:19:05Z |
| format | Article |
| id | doaj.art-f19caf02f4da4d539524af4bd7a834fa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T14:19:05Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f19caf02f4da4d539524af4bd7a834fa2023-05-05T05:13:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11293231129323Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DBTaciana MansoAnjana KushwahaNika AbdollahiPatrice DurouxVéronique GiudicelliSofia KossidaBackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immunosurveillance. Immunotherapies involving ICs either block or stimulate these pathways and enhance the efficiency of the immune system to recognize and attack cancer cells. In this way, the development of monoclonal antibodies (mAbs) targeting ICs has significant success in cancer treatment. Recently, a systematic description of the mechanisms of action (MOA) of the mAbs has been introduced in IMGT/mAb-DB, the IMGT® database dedicated to mAbs for therapeutic applications. The characterization of these antibodies provides a comprehensive understanding of how mAbs work in cancer.MethodsIn depth biocuration taking advantage of the abundant literature data as well as amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, allowed to define a standardized and consistent description of the MOA of mAbs targeting immune checkpoints in cancer therapy.ResultsA fine description and a standardized graphical representation of the MOA of selected mAbs are integrated within IMGT/mAb-DB highlighting two main mechanisms in cancer immunotherapy, either Blocking or Agonist. In both cases, the mAbs enhance cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune response (Immunostimulant effect) against tumor cells. On the one hand, mAbs targeting co-inhibitory receptors may have a functional Fc region to increase anti-tumor activity by effector properties that deplete Treg cells (Fc-effector function effect) or may have limited FcγR binding to prevent Teff cells depletion and reduce adverse events. On the other hand, agonist mAbs targeting co-stimulatory receptors may bind to FcγRs, resulting in antibody crosslinking (FcγR crosslinking effect) and substantial agonism.ConclusionIn IMGT/mAb-DB, mAbs for cancer therapy are characterized by their chains, domains and sequence and by several therapeutic metadata, including their MOA. MOAs were recently included as a search criterion to query the database. IMGT® is continuing standardized work to describe the MOA of mAbs targeting additional immune checkpoints and novel molecules in cancer therapy, as well as expanding this study to other clinical domains.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1129323/fullIMGTmonoclonal antibodiesimmune checkpointsoncologyimmunotherapy |
| spellingShingle | Taciana Manso Anjana Kushwaha Nika Abdollahi Patrice Duroux Véronique Giudicelli Sofia Kossida Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB Frontiers in Immunology IMGT monoclonal antibodies immune checkpoints oncology immunotherapy |
| title | Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB |
| title_full | Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB |
| title_fullStr | Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB |
| title_full_unstemmed | Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB |
| title_short | Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB |
| title_sort | mechanisms of action of monoclonal antibodies in oncology integrated in imgt mab db |
| topic | IMGT monoclonal antibodies immune checkpoints oncology immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1129323/full |
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