Kim, Hyelim Son, Boram Seo, Eun U. Kwon, Miji Ahn, June Hong Shin, Heungsoo Song, Gyu Yong Park, Eun Ji Na, Dong Hee Cho, Seung-Woo Kim, Hong Nam Park, Hee Ho Lee, Wonhwa 2024-01-19T11:30:36Z 2024-01-19T11:30:36Z 2022-07-08 2022-09 2198-3844 https://pubs.kist.re.kr/handle/201004/114747 Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases gamma-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue-engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases. English Wiley-VCH Verlag Cleavage-Responsive Biofactory T Cells Suppress Infectious Diseases-Associated Hypercytokinemia Article 10.1002/advs.202201883 1 Advanced Science, v.9, no.26 Advanced Science 9 26 Y scie scopus 000815620300001 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article PROTEIN-C RECEPTOR SEPSIS THROMBIN ACTIVATION INHIBITION MORBIDITY COVID-19 STRESS LIVER GLA COVID-19 engineered blood vessel engineered T cell hypercytokinemia infectious disease