Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5

Paolo Durigutto, Paolo Macor, Federica Ziller, Luca De Maso, Fabio Fischetti, Roberto Marzari, Daniele Sblattero, Francesco Tedesco

Research output: Contribution to journalArticle

Abstract

Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.

Original languageEnglish
Article numbere58696
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 7 2013

Fingerprint

Complement C5
recombinant antibodies
arthritis
Neutralizing Antibodies
neutralization
Arthritis
complement
Rats
Antibodies
knees
rats
antibody formation
injection
Joints
DNA
Antibody Formation
antigens
Knee
antibodies
rheumatoid arthritis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5. / Durigutto, Paolo; Macor, Paolo; Ziller, Federica; De Maso, Luca; Fischetti, Fabio; Marzari, Roberto; Sblattero, Daniele; Tedesco, Francesco.

In: PLoS One, Vol. 8, No. 3, e58696, 07.03.2013.

Research output: Contribution to journalArticle

Durigutto, P, Macor, P, Ziller, F, De Maso, L, Fischetti, F, Marzari, R, Sblattero, D & Tedesco, F 2013, 'Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5', PLoS One, vol. 8, no. 3, e58696. https://doi.org/10.1371/journal.pone.0058696
Durigutto, Paolo ; Macor, Paolo ; Ziller, Federica ; De Maso, Luca ; Fischetti, Fabio ; Marzari, Roberto ; Sblattero, Daniele ; Tedesco, Francesco. / Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5. In: PLoS One. 2013 ; Vol. 8, No. 3.
@article{8c01452ce8d84e51ad46170c48b5b521,
title = "Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5",
abstract = "Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.",
author = "Paolo Durigutto and Paolo Macor and Federica Ziller and {De Maso}, Luca and Fabio Fischetti and Roberto Marzari and Daniele Sblattero and Francesco Tedesco",
year = "2013",
month = "3",
day = "7",
doi = "10.1371/journal.pone.0058696",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5

AU - Durigutto, Paolo

AU - Macor, Paolo

AU - Ziller, Federica

AU - De Maso, Luca

AU - Fischetti, Fabio

AU - Marzari, Roberto

AU - Sblattero, Daniele

AU - Tedesco, Francesco

PY - 2013/3/7

Y1 - 2013/3/7

N2 - Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.

AB - Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.

UR - http://www.scopus.com/inward/record.url?scp=84874731813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874731813&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0058696

DO - 10.1371/journal.pone.0058696

M3 - Article

C2 - 23505550

AN - SCOPUS:84874731813

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e58696

ER -