AbGn-168H   

GtoPdb Ligand ID: 10013

Synonyms: AbGn-168 | neihulizumab
Compound class: Antibody
Comment: AbGn-168H (neihulizumab) is a first-in-class, humanised anti-P-selectin glycoprotein 1 (PSGL-1) monoclonal antibody that is being developed by AbGenomics [2-3]. AbGn-168H targets the PSGL-1/P-selectin pathway that is involved in leukocyte recruitment to inflammatory sites. It blocks PSGL-1 expressed by activated T cells or NK cells, and inhibits their interaction with P-selectin on endothelial cells of the vasculature. AbGn-168H binds to a different epitope on P-selectin compared to the endogenous ligand PSGL-1 so it is not expected to interfere with the P-selectin-dependent recruitment of leukocytes that is essential for innate immunity. Nor does it alter aggregation of human platelets which express low levels of PSGL-1 [3].
Patent analysis identifies SEQ ID: 25 from AbGenomics' 2009 patent US7604800 [3] as the likely light chain variable region of AbGn-168H (DIQMTQSPSLSASVGDRVTITCRSSQSIVHNDGNTYFEWYQQKPGKAPKLLIYKVSNRFSGVPSRFSGSGSGTHFTLTISSLQPEDFATYYCFQGSYVPLTFGQGTKVEIK) and SEQ ID: 26 that is claimed in the same patent (EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVASISTGGSTYYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARDYDGYFDYWGQGTLVTVSS) is the likely heavy chain. AbGn-168H was humanised from a murine anti-PSGL-1 antibody referred to as 15A7 [3].
Immunopharmacology Comments
In addition to blocking the PSGL-1/P-selectin pathway that is involved in leukocyte recruitment to inflammatory sites, AbGn-168H also induces T cell and NK cell depletion/apoptosis. This novel mechanism of action has the potential to control pathologic T cell- or NK cell-mediated immune responses in autoimmune diseases, transplant rejection, allergic diseases and T cell cancer.
Immunopharmacology Disease
Disease X-Refs Comment References
Psoriasis Disease Ontology: DOID:8893
Phase 2 clinical evaluation of AbGn-168H in patients with moderate to severe chronic plaque psoriasis (NCT01855880) and active psoriatic arthritis (NCT02267642) has been completed, but results have not yet been published (July 2018).