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journal article·2022-09Open access

Cleavage‐Responsive Biofactory T Cells Suppress Infectious Diseases‐Associated Hypercytokinemia

Hyelim Kim, Boram Son, Eun U Seo, Miji Kwon, June Hong Ahn, Heungsoo Shin, Gyu Yong Song, Eun Ji Park, Dong Hee Na, Seung‐Woo Cho, Hong Nam Kim, Hee Ho Park, Wonhwa Lee

Advanced Science· Volume 9· Issue 26
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Source abstract

Abstract

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 γ‐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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Research context

OpenAlex topics: Antimicrobial Peptides and Activities · Peptidase Inhibition and Analysis · CAR-T cell therapy research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul 02792 Republic of Korea

Department of Biotechnology Yonsei University Seoul 03722 Republic of Korea

Department of Bioengineering Hanyang University Seoul 04763 Republic of Korea

Division of Bio‐Medical Science and Technology (KIST School) Korea University of Science and Technology (UST) Seoul 02792 Republic of Korea

Department of Smart Health Science and Technology Kangwon National University Chuncheon 24341 Republic of Korea

Division of Pulmonology and Allergy Department of Internal Medicine College of Medicine Yeungnam University and Regional Center for Respiratory Diseases Yeungnam University Medical Center Daegu 42415 Republic of Korea

College of Pharmacy Chungnam National University Daejeon 34134 Republic of Korea

AREZ Co. Ltd Daejeon 34134 Republic of Korea

D&D Pharmatech Seongnam 13486 Republic of Korea

College of Pharmacy Chung‐Ang University Seoul 06974 Republic of Korea

School of Mechanical Engineering Yonsei University Seoul 03722 Republic of Korea

Yonsei‐KIST Convergence Research Institute Yonsei University Seoul 03722 Republic of Korea

BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader Hanyang University Seoul 04763 Republic of Korea

Research Institute for Convergence of Basic Science Hanyang University Seoul 04763 Republic of Korea

Department of Chemistry Sungkyunkwan University Suwon 16419 Republic of Korea

Funding

National Research Foundation of Korea

References (48)

Show source-provided references
1. 10.1056/NEJMoa210907210.1056/NEJMoa2109072 ↗
2. 10.1016/S1473-3099(21)00558-210.1016/S1473-3099(21)00558-2 ↗
3. 10.1084/jem.2006037510.1084/jem.20060375 ↗
4. 10.4161/viru.2704510.4161/viru.27045 ↗
5. 10.1186/s13054-018-2052-710.1186/s13054-018-2052-7 ↗
6. 10.1016/S0140-6736(20)30628-010.1016/S0140-6736(20)30628-0 ↗
7. 10.1016/S2213-2600(20)30161-210.1016/S2213-2600(20)30161-2 ↗
8. 10.1016/S2213-2600(20)30165-X10.1016/S2213-2600(20)30165-X ↗
9. 10.1016/S0140-6736(20)30183-510.1016/S0140-6736(20)30183-5 ↗
10. 10.1016/j.bmc.2017.06.05210.1016/j.bmc.2017.06.052 ↗
11. 10.1016/j.jconrel.2011.09.09210.1016/j.jconrel.2011.09.092 ↗
12. 10.1056/NEJM20010308344100910.1056/NEJM200103083441009 ↗
13. 10.1182/blood-2006-09-00300410.1182/blood-2006-09-003004 ↗
14. 10.1016/S0021-9258(19)47415-210.1016/S0021-9258(19)47415-2 ↗
15. 10.1002/j.1460-2075.1996.tb01073.x10.1002/j.1460-2075.1996.tb01073.x ↗
16. U. Food D. Administration Drug Safety and Availability Washington DC2011 p.25.
17. 10.1182/blood-2013-09-52100510.1182/blood-2013-09-521005 ↗
18. 10.1007/s00018-011-0825-010.1007/s00018-011-0825-0 ↗
19. 10.1111/j.1538-7836.2007.02347.x10.1111/j.1538-7836.2007.02347.x ↗
20. 10.1161/ATVBAHA.117.30992610.1161/ATVBAHA.117.309926 ↗
21. 10.1002/emmm.20110014610.1002/emmm.201100146 ↗
22. 10.1074/jbc.275.8.603810.1074/jbc.275.8.6038 ↗
23. 10.1182/blood-2007-06-09665110.1182/blood-2007-06-096651 ↗
24. 10.1074/jbc.M60050620010.1074/jbc.M600506200 ↗
25. 10.1182/blood-2004-10-398510.1182/blood-2004-10-3985 ↗
26. 10.1160/TH08-02-012710.1160/TH08-02-0127 ↗
27. 10.1002/adma.20150309310.1002/adma.201503093 ↗
28. 10.1007/s00134-011-2171-y10.1007/s00134-011-2171-y ↗
29. 10.1038/nprot.2008.21410.1038/nprot.2008.214 ↗
30. 10.1007/978-1-62703-481-4_1510.1007/978-1-62703-481-4_15 ↗
31. Annuk M. · J. Nephrol. · 2005 · 18 · 721
32. 10.1084/jem.123.2.36510.1084/jem.123.2.365 ↗
33. Tsujimoto Y. · Cochrane Database Syst Rev · 2019
34. 10.4161/15384101.2014.96505410.4161/15384101.2014.965054 ↗
35. 10.1073/pnas.06200189910.1073/pnas.062001899 ↗
36. 10.1021/acs.jmedchem.7b0031810.1021/acs.jmedchem.7b00318 ↗
37. 10.1038/srep3661710.1038/srep36617 ↗
38. 10.1016/j.biopha.2018.04.02510.1016/j.biopha.2018.04.025 ↗
39. 10.1002/adfm.20200611010.1002/adfm.202006110 ↗
40. 10.1016/S2213-2600(20)30079-510.1016/S2213-2600(20)30079-5 ↗
41. 10.1038/s41577-020-0402-610.1038/s41577-020-0402-6 ↗
42. 10.1038/s41586-020-2550-z10.1038/s41586-020-2550-z ↗
43. Park H. H. · Sci. Adv. · 2020 · 6 · 31
44. 10.1126/sciimmunol.abe478210.1126/sciimmunol.abe4782 ↗
45. 10.1001/jama.2016.028710.1001/jama.2016.0287 ↗
46. 10.1063/1.491750810.1063/1.4917508 ↗
47. 10.1007/s00109-013-1081-610.1007/s00109-013-1081-6 ↗
48. Sun F. · Bio Protoc. · 2017 · 7 · 10