Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody.
Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), a homotypic cell adhesion molecule glycoprotein with apical expression on normal epithelial cells and activated lymphocytes, is overexpressed on many tumors and acts as an inhibitory receptor on NK cells, preventing their killing of CEACAM...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295345&type=printable |
| _version_ | 1797299640230477824 |
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| author | Michela Centonze Valentina Fiori Maciej Kujawski Lin Li Patty Wong Lindsay Williams Tomas Di Mambro Sabrina Dominici Angelo Sparti John E Shively Mauro Magnani |
| author_facet | Michela Centonze Valentina Fiori Maciej Kujawski Lin Li Patty Wong Lindsay Williams Tomas Di Mambro Sabrina Dominici Angelo Sparti John E Shively Mauro Magnani |
| author_sort | Michela Centonze |
| collection | DOAJ |
| description | Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), a homotypic cell adhesion molecule glycoprotein with apical expression on normal epithelial cells and activated lymphocytes, is overexpressed on many tumors and acts as an inhibitory receptor on NK cells, preventing their killing of CEACAM1 positive tumors. Production of humanized anti-CEACAM1 antibodies to block the inhibitory activity of CEACAM1 for immunotherapy and immunoimaging. Starting from a scFv, a fully human intact anti-CEACAM1 (DIA 12.3) that recognizes the N-terminal domain of CEACAM1 was developed and shown to bind CEACAM1 positive tumor cells and enhanced NK cell killing of CEACAM1 positive targets. DIA 12.3 bound to human neutrophils without activation, indicating they would be safe for human use. DIA 12.3 exhibited some cross-reactivity to CEACAM5, a tumor marker with high sequence homology to the N-terminal domain of CEACAM1. CEACAM1 PET imaging with 64Cu-COTA-DIA 12.3 showed excellent imaging of CEACAM1 positive tumors with reduced binding to CEACAM5 tumors. Based on its immunoinhibitory an immunoimaging activities, DIA 12.3 shows promise for therapeutic studies in man. |
| first_indexed | 2024-03-07T22:53:35Z |
| format | Article |
| id | doaj.art-b51ad4ff63384ac8a4df3e97495290ac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-07T22:53:35Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b51ad4ff63384ac8a4df3e97495290ac2024-02-23T05:31:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01192e029534510.1371/journal.pone.0295345Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody.Michela CentonzeValentina FioriMaciej KujawskiLin LiPatty WongLindsay WilliamsTomas Di MambroSabrina DominiciAngelo SpartiJohn E ShivelyMauro MagnaniCarcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), a homotypic cell adhesion molecule glycoprotein with apical expression on normal epithelial cells and activated lymphocytes, is overexpressed on many tumors and acts as an inhibitory receptor on NK cells, preventing their killing of CEACAM1 positive tumors. Production of humanized anti-CEACAM1 antibodies to block the inhibitory activity of CEACAM1 for immunotherapy and immunoimaging. Starting from a scFv, a fully human intact anti-CEACAM1 (DIA 12.3) that recognizes the N-terminal domain of CEACAM1 was developed and shown to bind CEACAM1 positive tumor cells and enhanced NK cell killing of CEACAM1 positive targets. DIA 12.3 bound to human neutrophils without activation, indicating they would be safe for human use. DIA 12.3 exhibited some cross-reactivity to CEACAM5, a tumor marker with high sequence homology to the N-terminal domain of CEACAM1. CEACAM1 PET imaging with 64Cu-COTA-DIA 12.3 showed excellent imaging of CEACAM1 positive tumors with reduced binding to CEACAM5 tumors. Based on its immunoinhibitory an immunoimaging activities, DIA 12.3 shows promise for therapeutic studies in man.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295345&type=printable |
| spellingShingle | Michela Centonze Valentina Fiori Maciej Kujawski Lin Li Patty Wong Lindsay Williams Tomas Di Mambro Sabrina Dominici Angelo Sparti John E Shively Mauro Magnani Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. PLoS ONE |
| title | Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. |
| title_full | Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. |
| title_fullStr | Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. |
| title_full_unstemmed | Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. |
| title_short | Development and characterization of DIA 12.3, a fully human intact anti-CEACAM1 monoclonal antibody. |
| title_sort | development and characterization of dia 12 3 a fully human intact anti ceacam1 monoclonal antibody |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295345&type=printable |
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