Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I complex Demonstrates the Antitumor Efficacy of Hapten-Based Strategies.

Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Unfortunately, tumor-specific antigens remain challenging to identify and target. Recent work established that inhibitor-modified peptide adducts derived from KRAS G12C are competent for antigen presentation via MHC I and can be targeted by antibody-based therapeutics, offering a means to directly target an intracellular oncoprotein at the cell surface with combination therapies.

Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens Using Positron Emission Tomography.

Understanding how the host immune system engages complex pathogens is essential to developing therapeutic strategies to overcome their virulence. While granzymes are well understood to trigger apoptosis in infected host cells or bacteria, less is known about how the immune system mobilizes individual granzyme species to combat diverse pathogens. Toward the goal of studying individual granzyme function directly , we previously developed a new class of radiopharmaceuticals termed "restricted interaction peptides (RIPs)" that detect biochemically active endoproteases using positron emission tomography (PET).