Eric N Aguilar, Satish Sagar, Brandy R Murray, Christabelle Rajesh, Eric K Lei, Sarah A Michaud, David R Goodlett, Thomas C Caffrey, Paul M Grandgenett, Benjamin Swanson, Teresa M Brooks, Adrian R Black, Henk van Faassen, Greg Hussack, Kevin A Henry, Michael A Hollingsworth, Cory L Brooks, Prakash Radhakrishnan
Mucin-16 (MUC16) is a target for antibody-mediated immunotherapy in pancreatic ductal adenocarcinoma (PDAC) amongst other malignancies. The MUC16 specific monoclonal antibody AR9.6 has shown promise for PDAC immunotherapy and imaging. Here, we report the structural and biological characterization of the humanized AR9.6 antibody (huAR9.6). The structure of huAR9.6 was determined in complex with a MUC16 SEA (Sea urchin sperm, Enterokinase, Agrin) domain. Binding of huAR9.6 to recombinant, shed, and cell-surface MUC16 was characterized, and anti-PDAC activity was evaluated in vitro and in vivo...
February 23, 2024: Molecular Cancer Therapeutics