Trang T Vu, Kyeongmin Kim, Millennium Manna, Justin Thomas, Bryan Remaily, Emma J Montgomery, Travis Costa, Lauren Granchie, Zhiliang Xie, Yizhen Guo, Min Chen, Alyssa Marie M Castillo, Samuel K Kulp, Xiaokui Mo, Sridhar Nimmagadda, Paul Gregorevic, Dwight H Owen, Latha P Ganesan, Thomas A Mace, Christopher C Coss, Mitch A Phelps
High baseline clearance of immune checkpoint inhibitors (ICIs), independent of dose or systemic exposure, is associated with cachexia and poor outcomes in cancer patients. Mechanisms linking ICI clearance, cachexia and ICI therapy failure are unknown. Here, we evaluate in four murine models and across multiple antibodies whether altered baseline catabolic clearance of administered antibody requires a tumor and/or cachexia and whether medical reversal of cachexia phenotype can alleviate altered clearance. Key findings include mild cachexia phenotype and lack of elevated pembrolizumab clearance in the MC38 tumor-bearing model...
December 23, 2023: Pharmacological Research: the Official Journal of the Italian Pharmacological Society