1186 Engineering bispecific dual-antagonist antibodies for novel cancer therapies

• DOI: 10.1136/jitc-2023-sitc2023.1186
• Publication Date: 2023-10-31T14:43:51Z
• Authors: Ankita Srivastava; Tracy Charlton; Ranveer Jayani; Omer Keinan; Arvin Akoopie; Jonah Rainey; Jacek Ostrowski
• Keywords: Bispecific antibody

<h3>Background</h3> Bispecific antibodies have the potential to unlock novel biology and elicit unique functionalities. There is still an unmet need for effective selective therapeutics cancer treatment. Here, we present discovery of diverse panels lead-quality against two targets reformatting them into bispecifics development dual antagonist therapeutic antibody. <h3>Methods</h3> Binders derived from immunizing AlivaMab^® Mouse were engineered as bispecific with Fab scFv substrates using standard knob-into-hole heterodimerization approach. The characterized by ELISA FACS assays target binding blocking. Target dependent inhibition cell proliferation was also investigated. Developability assessment expression, purity, thermal stability, polyspecificity<b>,</b> accelerated stability performed. <h3>Results</h3> We demonstrated that dual-antagonist are capable blocking both targets, resulting in when bound antigens showed superior activity clinical comparators. Selected lead met developability acceptance criteria good serum studies. <h3>Conclusions</h3> A broad panel molecularly highly potent specific binders discovered can bind surface soluble forms. Function-first screening antibody matrix delivered quality leads validated cell-based assays. Early profiling format, domain order sequence matter product quality, high expression titer, potency selected move forward. <h3>Acknowledgements</h3> Larry Green, Stacey Borders, Mohammad Abu Odeh, Soneela Ramesh, Crystal Bantados, Jane Seagal