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Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity
- Source :
- Frontiers in Oncology, Frontiers in Oncology, Vol 11 (2021)
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Cancer Research
medicine.drug_class
medicine.medical_treatment
Monoclonal antibody
Immune system
Blocking antibody
medicine
NK cell
RC254-282
Original Research
biology
Chemistry
human Siglec 9
SIGLEC
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunotherapy
respiratory system
Immunosurveillance
ovarian cancer
Oncology
Humanized mouse
biology.protein
Cancer research
monoclonal antibodies
immunotherapy
Antibody
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in oncology
- Accession number :
- edsair.doi.dedup.....afc580f61c6b65e097c547d8cd40fc4c