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Your search keyword '"Kwiecien, Jacek M."' showing total 2 results
Start Over Author "Kwiecien, Jacek M." Topic immune modulation
2 results on '"Kwiecien, Jacek M."'

1. Deriving Immune Modulating Drugs from Viruses-A New Class of Biologics

Author

Yaron, Jordan R., Liqiang, zhang, Guo, Qiuyun, Burgin, Michelle, Schutz, Lauren N., Awo, Enkidia, Wise, Lyn, Krause, Kurt L., Ildefonso, Cristhian J., Kwiecien, Jacek M., Juby, Michael, Rahman, Masmudur M., Chen, Hao, Moye, Richard W., Alcamí, Antonio, McFadden, Grant, Lucas, Alexandra R., American Heart Association, University of Florida, and Biodesign Institute (US)

Subjects
Serpin, Biologic, Chemokine, viruses, Protein, chemokine binding protein, Immune modulation, growth factor, Interleukin, Therapeutic, Cytokine, Virus
Abstract

Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as natural sources for immune modulators remains in the early stages of development. Viruses have evolved complex, highly e ective approaches for immune evasion. Originally developed for protection against host immune responses, viral immune-modulating proteins are extraordinarily potent, often functioning at picomolar concentrations. These complex viral intracellular parasites have “performed the R&D”, developing highly e ective immune evasive strategies over millions of years. These proteins provide a new and natural source for immune-modulating therapeutics, similar in many ways to penicillin being developed from mold or streptokinase from bacteria. Virus-derived serine proteinase inhibitors (serpins), chemokine modulating proteins, complement control, inflammasome inhibition, growth factors (e.g., viral vascular endothelial growth factor) and cytokine mimics (e.g., viral interleukin 10) and/or inhibitors (e.g., tumor necrosis factor) have now been identified that target central immunological response pathways. We review here current development of virus-derived immune-modulating biologics with effcacy demonstrated in pre-clinical or clinical studies, focusing on pox and herpesviruses-derived immune-modulating therapeutics American Heart Association (17GRNT33460327), University of Florida Gatorade Fund (00115070) and start-up funds from the Biodesign Institute at Arizona State University

Published
2020

2. Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function.

Author

Kwiecien, Jacek M., Zhang, Liqiang, Yaron, Jordan R., Schutz, Lauren N., Kwiecien-Delaney, Christian J., Awo, Enkidia A., Burgin, Michelle, Dabrowski, Wojciech, and Lucas, Alexandra R.

Subjects
*SPINAL cord injuries, *CRUSH syndrome, *TISSUES
Abstract

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI. [ABSTRACT FROM AUTHOR]

Published
2020
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