Viral serpin therapeutics: From concept to clinic

Hao Chen, Donghang Zheng, Jennifer Davids, Mee Yong Bartee, Erbin Dai, Liying Liu, Lyubomir Petrov, Colin Macaulay, Robert Thoburn, Eric Sobel, Richard Moyer, Douglas McFadden, Alexandra Lucas

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. Finally, we provide an overview of our findings from a recent, successful clinical trial of the secreted myxomaviral serpin, Serp-1, in patients with unstable inflammatory coronary arterial disease.

Original languageEnglish (US)
Pages (from-to)301-329
Number of pages29
JournalMethods in Enzymology
Volume499
DOIs
StatePublished - Jun 24 2011
Externally publishedYes

Fingerprint

Serpins
Viruses
Anti-Inflammatory Agents
Therapeutics
Myxoma virus
Clinical Trials
Serine Proteinase Inhibitors
Immunologic Factors
Coronary Disease
Animals
Animal Models

Keywords

  • Adhesion assay
  • Clinical trial
  • Flow cytometry
  • Immunotherapeutics
  • Mouse angioplasty model
  • PCR arrays
  • SERP-1
  • SERP-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Chen, H., Zheng, D., Davids, J., Bartee, M. Y., Dai, E., Liu, L., ... Lucas, A. (2011). Viral serpin therapeutics: From concept to clinic. Methods in Enzymology, 499, 301-329. https://doi.org/10.1016/B978-0-12-386471-0.00015-8

Viral serpin therapeutics : From concept to clinic. / Chen, Hao; Zheng, Donghang; Davids, Jennifer; Bartee, Mee Yong; Dai, Erbin; Liu, Liying; Petrov, Lyubomir; Macaulay, Colin; Thoburn, Robert; Sobel, Eric; Moyer, Richard; McFadden, Douglas; Lucas, Alexandra.

In: Methods in Enzymology, Vol. 499, 24.06.2011, p. 301-329.

Research output: Contribution to journalArticle

Chen, H, Zheng, D, Davids, J, Bartee, MY, Dai, E, Liu, L, Petrov, L, Macaulay, C, Thoburn, R, Sobel, E, Moyer, R, McFadden, D & Lucas, A 2011, 'Viral serpin therapeutics: From concept to clinic', Methods in Enzymology, vol. 499, pp. 301-329. https://doi.org/10.1016/B978-0-12-386471-0.00015-8
Chen H, Zheng D, Davids J, Bartee MY, Dai E, Liu L et al. Viral serpin therapeutics: From concept to clinic. Methods in Enzymology. 2011 Jun 24;499:301-329. https://doi.org/10.1016/B978-0-12-386471-0.00015-8
Chen, Hao ; Zheng, Donghang ; Davids, Jennifer ; Bartee, Mee Yong ; Dai, Erbin ; Liu, Liying ; Petrov, Lyubomir ; Macaulay, Colin ; Thoburn, Robert ; Sobel, Eric ; Moyer, Richard ; McFadden, Douglas ; Lucas, Alexandra. / Viral serpin therapeutics : From concept to clinic. In: Methods in Enzymology. 2011 ; Vol. 499. pp. 301-329.
@article{fbbe26dc855a4f28a2509d417769e615,
title = "Viral serpin therapeutics: From concept to clinic",
abstract = "Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. Finally, we provide an overview of our findings from a recent, successful clinical trial of the secreted myxomaviral serpin, Serp-1, in patients with unstable inflammatory coronary arterial disease.",
keywords = "Adhesion assay, Clinical trial, Flow cytometry, Immunotherapeutics, Mouse angioplasty model, PCR arrays, SERP-1, SERP-2",
author = "Hao Chen and Donghang Zheng and Jennifer Davids and Bartee, {Mee Yong} and Erbin Dai and Liying Liu and Lyubomir Petrov and Colin Macaulay and Robert Thoburn and Eric Sobel and Richard Moyer and Douglas McFadden and Alexandra Lucas",
year = "2011",
month = "6",
day = "24",
doi = "10.1016/B978-0-12-386471-0.00015-8",
language = "English (US)",
volume = "499",
pages = "301--329",
journal = "Methods",
issn = "1046-2023",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Viral serpin therapeutics

T2 - From concept to clinic

AU - Chen, Hao

AU - Zheng, Donghang

AU - Davids, Jennifer

AU - Bartee, Mee Yong

AU - Dai, Erbin

AU - Liu, Liying

AU - Petrov, Lyubomir

AU - Macaulay, Colin

AU - Thoburn, Robert

AU - Sobel, Eric

AU - Moyer, Richard

AU - McFadden, Douglas

AU - Lucas, Alexandra

PY - 2011/6/24

Y1 - 2011/6/24

N2 - Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. Finally, we provide an overview of our findings from a recent, successful clinical trial of the secreted myxomaviral serpin, Serp-1, in patients with unstable inflammatory coronary arterial disease.

AB - Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. Finally, we provide an overview of our findings from a recent, successful clinical trial of the secreted myxomaviral serpin, Serp-1, in patients with unstable inflammatory coronary arterial disease.

KW - Adhesion assay

KW - Clinical trial

KW - Flow cytometry

KW - Immunotherapeutics

KW - Mouse angioplasty model

KW - PCR arrays

KW - SERP-1

KW - SERP-2

UR - http://www.scopus.com/inward/record.url?scp=79959336314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959336314&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-386471-0.00015-8

DO - 10.1016/B978-0-12-386471-0.00015-8

M3 - Article

C2 - 21683260

AN - SCOPUS:79959336314

VL - 499

SP - 301

EP - 329

JO - Methods

JF - Methods

SN - 1046-2023

ER -