Novel biologics targeting Siglec-8 to treat eosinophil-driven diseases Fully human mAbs, bispecific antibodies, and NK CARs that target Siglec-8. Siglec-8 is a transmembrane protein expressed on mature eosinophils, mast cells, and (to a lesser degree) basophils. Excessive eosinophil and mast cell activity have been implicated in the pathology of multiple diseases, including atopic dermatitis, chronic rhinosinusitis, chronic urticaria, and eosinophilic esophagitis. Dr. Roland Walter’s group in the Clinical Research Division at Fred Hutch has developed multiple fully human Siglec-8 mAbs, bispecific molecules that can engage T cells and Siglec-8, and NK CARs that target Siglec-8. These biologics could be used as targeted therapies for patients with eosinophil or mast cell driven disease. <ul> <li>Reduction of eosinophil count and inhibition of mast cell activity</li> <li>Targeted treatment of any disease in which excessive eosinophil or mast cell activity is implicated, such as eosinophilic esophagitis, chronic rhinosinusitis with nasal polyposis, atopic dermatitis, and chronic urticaria.</li> <li>Research tool to investigate Siglec-8 signaling and immune interactions (via the bispecific molecules).</li> </ul> <ul> <li>Highly targeted: Siglec-8 is only expressed on certain cell types, limiting the risk of off-target effects</li> <li>Fully human antibody offer reduced immunogenicity and higher half-life</li> </ul> <ul> <li>Roland B. Walter, MD PhD MS, Professor, Clinical Research Division, José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research</li> </ul> Preclinical in vitro experiments completed Provisional patent applications filed 22-167 Walter Siglec-8 NCS - July 18, 2023.pdf |Therapeutic | hybridoma | antibody | immune oncology | Siglec-8 | rare/orphan diseases | eosinophils | CARs | NK | cell therapy siglec8-mabs-cars