AUTHOR=Choi Hyeree , Ho Michelle , Adeniji Opeyemi S. , Giron Leila , Bordoloi Devivasha , Kulkarni Abhijeet J. , Puchalt Alfredo Perales , Abdel-Mohsen Mohamed , Muthumani Kar 

TITLE=Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.778989

DOI=10.3389/fonc.2021.778989

ISSN=2234-943X

ABSTRACT=<p>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 <italic>in vitro</italic> cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, <italic>in vivo</italic> 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.</p>