Neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) are structurally related enzymes that are stored within the neutrophil cytoplasmic azurophilic granules and are collectively known as neutrophil serine proteases (NSPs). NSPs are synthesized as inactive pre-pro-proteins during granulocyte development and are converted to active proteins by dipeptidyl peptidase 1 (DPP1) during the neutrophil maturation process in bone marrow. NSPs play a foremost role in pathogen destruction, contributing to inflammatory regulation and modulation. However, dysregulated NSP activities contribute to damaging inflammation and tissue matrix destruction and is linked to chronic inflammatory and autoimmune diseases as well as cancer progression. Given their involvement in certain disease pathologies and correlation with disease severity, NSP and DPP1 inhibitors are being pursued as pharmaceutical targets. We describe the challenges in translating these NSP biomarkers preclinically in rodents to human, focusing on species differences, sampling, and technical challenges.
Learning Objectives:
Understand the challenges in translating biomarker assays from preclinical studies to the clinic
Design and develop solutions to overcome the biomarker analytical and technical challenges
Recognize the benefit of quantifying clinical biomarkers to identify the appropriate patients to enroll in clinical trials as well as those who respond to therapy
