Production and characterisation of a set of monoclonal antibodies against tissue-type plasminogen activator (t-PA) |
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| Affiliation: | 1. Highway College, Chang’an University, Xi’an, Shaanxi, China;2. College of Civil Engineering, Xi''an University of Architecture and Technology, Xi’an, Shaanxi, China;1. Department of Environmental Applied Chemistry, Faculty of Engineering, University of Toyama, Toyama, 930-8555, Japan;2. Department of Chemistry and Bioengineering, Faculty of Engineering, Iwate University, Morioka, Iwate, 020-8551, Japan;1. Advocate Research Institute, Advocate Health Care, Downers Grove, IL;2. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada;3. Department of Pediatrics, University of Antioquia, Medellin, Colombia;4. Division of Hematology, Medicine and Pathology, Duke University Medical Center, Durham, NC;5. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT;6. Department of Medicine, McMaster University, Hamilton, ON, Canada;7. Department of Obstetrics and Gynecology, The First I. M. Sechenov Moscow State Medical University, Moscow, Russia;8. Department of Surgery, University of California Davis, Sacramento, CA;9. Division of General Internal Medicine, Department of Medicine, University of Florida, Gainesville, FL;10. Malcom Randall Veterans Affairs Medical Center, Gainesville, FL;11. Clinical Pharmacy Anticoagulation Service, Kaiser Permanente Colorado, Aurora, CO;12. Guang'' anmen Hospital, China Academy of Chinese Medical Science, Xicheng District, Beijing, China |
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| Abstract: | ![]()
To generate bispecific monoclonal antibodies, reactive to both fibrin and tissue-type plasminogen activator (t-PA), we planned to generate anti-t-PA monoclonal antibodies (mAb) which eliminate negative aspects of t-PA such as the inhibition by plasminogen activator inhibitor-type 1 (PAI-1) and the rapid clearance of t-PA. Here we report on the isolation and characterisation of a set of 13 mAb against t-PA, some of which meet the above requirements. Apart from their potential in the production of bispecific antibodies, these and the other mAb can be useful in structure-function analysis and a variety of other applications.Experiments involving PAI-1 showed that one mAB (12-5-3) reacts only with free t-PA, and prevents the subsequent binding of PAI-1 to mAb-bound t-PA. In vitro studies on the receptor mediated uptake of t-PA by hepatic cells, showed that one mAb (1-3-1) specifically inhibited the association of t-PA with liver endothelial cells. Other tests showed that mAb 7-8-4 and 12-5-3, but not 1-3-1, inhibited in vitro the enzymatic activity of t-PA.On the basis of these and other observations, we conclude that especially mAb 1-3-1, and in vivo possibly 7-8-4 and 12-5-3 may be good candidates for incorporation in bispecific monoclonal antibodies. |
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