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...

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Autores principales:	Hyeree Choi, Michelle Ho, Opeyemi S. Adeniji, Leila Giron, Devivasha Bordoloi, Abhijeet J. Kulkarni, Alfredo Perales Puchalt, Mohamed Abdel-Mohsen, Kar Muthumani
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	human Siglec 9 NK cell monoclonal antibodies ovarian cancer immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c25bf30ad0a244629991b3e95285bea3
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spelling	oai:doaj.org-article:c25bf30ad0a244629991b3e95285bea32021-11-19T06:26:14ZDevelopment of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity2234-943X10.3389/fonc.2021.778989https://doaj.org/article/c25bf30ad0a244629991b3e95285bea32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.778989/fullhttps://doaj.org/toc/2234-943XSialic 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.Hyeree ChoiMichelle HoOpeyemi S. AdenijiLeila GironDevivasha BordoloiAbhijeet J. KulkarniAlfredo Perales PuchaltMohamed Abdel-MohsenKar MuthumaniFrontiers Media S.A.articlehuman Siglec 9NK cellmonoclonal antibodiesovarian cancerimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human Siglec 9 NK cell monoclonal antibodies ovarian cancer immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	human Siglec 9 NK cell monoclonal antibodies ovarian cancer immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	development of siglec-9 blocking antibody to enhance anti-tumor immunity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c25bf30ad0a244629991b3e95285bea3
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Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity

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