Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity
Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.778989/full |
| _version_ | 1819002641856856064 |
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| author | Hyeree Choi Michelle Ho Opeyemi S. Adeniji Leila Giron Devivasha Bordoloi Abhijeet J. Kulkarni Alfredo Perales Puchalt Mohamed Abdel-Mohsen Kar Muthumani |
| author_facet | Hyeree Choi Michelle Ho Opeyemi S. Adeniji Leila Giron Devivasha Bordoloi Abhijeet J. Kulkarni Alfredo Perales Puchalt Mohamed Abdel-Mohsen Kar Muthumani |
| author_sort | Hyeree Choi |
| collection | DOAJ |
| description | Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The in vitro cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, in vivo testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression. |
| first_indexed | 2024-12-20T23:08:20Z |
| format | Article |
| id | doaj.art-c25bf30ad0a244629991b3e95285bea3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T23:08:20Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c25bf30ad0a244629991b3e95285bea32022-12-21T19:23:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.778989778989Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor ImmunityHyeree ChoiMichelle HoOpeyemi S. AdenijiLeila GironDevivasha BordoloiAbhijeet J. KulkarniAlfredo Perales PuchaltMohamed Abdel-MohsenKar MuthumaniSialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The in vitro cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, in vivo testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.https://www.frontiersin.org/articles/10.3389/fonc.2021.778989/fullhuman Siglec 9NK cellmonoclonal antibodiesovarian cancerimmunotherapy |
| spellingShingle | Hyeree Choi Michelle Ho Opeyemi S. Adeniji Leila Giron Devivasha Bordoloi Abhijeet J. Kulkarni Alfredo Perales Puchalt Mohamed Abdel-Mohsen Kar Muthumani Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity Frontiers in Oncology human Siglec 9 NK cell monoclonal antibodies ovarian cancer immunotherapy |
| title | Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity |
| title_full | Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity |
| title_fullStr | Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity |
| title_full_unstemmed | Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity |
| title_short | Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity |
| title_sort | development of siglec 9 blocking antibody to enhance anti tumor immunity |
| topic | human Siglec 9 NK cell monoclonal antibodies ovarian cancer immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.778989/full |
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