Cleavage-Responsive Biofactory T Cells Suppress Infectious Diseases-Associated Hypercytokinemiaopen access
- Authors
- Kim, H[Kim, Hyelim]; Son, B[Son, Boram]; Seo, EU[Seo, Eun U.]; Kwon, M[Kwon, Miji]; Ahn, JH[Ahn, June Hong]; Shin, H[Shin, Heungsoo]; Song, GY[Song, Gyu Yong]; Park, EJ[Park, Eun Ji]; Na, DH[Na, Dong Hee]; Cho, SW[Cho, Seung-Woo]; Kim, HN[Kim, Hong Nam]; Park, HH[Park, Hee Ho]; Lee, W[Lee, Wonhwa]
- Issue Date
- Sep-2022
- Publisher
- WILEY
- Keywords
- COVID-19; engineered blood vessel; engineered T cell; hypercytokinemia; infectious disease
- Citation
- ADVANCED SCIENCE, v.9, no.26
- Indexed
- SCIE
SCOPUS
- Journal Title
- ADVANCED SCIENCE
- Volume
- 9
- Number
- 26
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/98110
- DOI
- 10.1002/advs.202201883
- ISSN
- 2198-3844
- Abstract
- 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.
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- Appears in
Collections - Graduate School > Chemistry > 1. Journal Articles
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