Abstract LB060: Engineering KRAS mutation-specific affinity binders: A new frontier in cancer research

Abstract

Abstract Cancer is a complex disease involving genetic and proteomic dysregulation. Better understanding of this disease requires precise tools to analyze how cells change from a normal to a diseased state. Among the genes implicated in cancer, the checkpoint inhibitor KRAS is notable for its frequent cancer causing mutations. These mutations, especially in glycine codon 12, are a driving force in several cancers, including those of the pancreas, lung, and colon. Recently, researchers have made significant strides in treating one variant, targeting G12C, using small molecules. However, other mutations, including the G12D and G12V variants, which are more common in disease, still lack targeted treatments. To overcome this challenge, we are using a unique immunization and screening strategy to identify a series of KRAS mutant-specific binders. These affinity binders, targeting the wild-type glycine and variants like G12D, G12S, G12C, G12A, G12R, and G12V, are being designed for research purposes to dissect cancer pathways and understand the spatial organization of cancer cells. They may also hold potential for clinical use as tools for prognosis and therapy. Deep characterization of these and other potentially widely used tools will be critical for advancing their uptake in the laboratory and clinic. Citation Format: Ramon Serrano, Ryan Wallace, Sergei Bibikov, Michael Weiner, Kevin J. Harvey. Engineering KRAS mutation-specific affinity binders: A new frontier in cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB060.