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In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats

BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This...

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Autores principales: Gearing, D.P., Huebner, M., Virtue, E.R., Knight, K., Hansen, P., Lascelles, B.D.X., Gearing, R.P., Drew, A.C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094543/
https://www.ncbi.nlm.nih.gov/pubmed/27306920
http://dx.doi.org/10.1111/jvim.13985
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author Gearing, D.P.
Huebner, M.
Virtue, E.R.
Knight, K.
Hansen, P.
Lascelles, B.D.X.
Gearing, R.P.
Drew, A.C.
author_facet Gearing, D.P.
Huebner, M.
Virtue, E.R.
Knight, K.
Hansen, P.
Lascelles, B.D.X.
Gearing, R.P.
Drew, A.C.
author_sort Gearing, D.P.
collection PubMed
description BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This study describes the design and characterization of a fully felinized anti‐NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self‐resolving, acute inflammation model were investigated in cats. ANIMALS: Thirty‐eight cats at a research colony at Charles River Laboratories, Ireland. METHODS: Felinized anti‐NGF mAb, NV‐02, was produced using a complementary DNA (cDNA)‐based method (PETization). Purified NV‐02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin‐induced inflammatory pain. RESULTS: Anti‐NGF mAb, NV‐02 neutralized NGF with high affinity and potency and did not bind complement. NV‐02‐administered SC had a plasma half‐life of 7–15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV‐02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: The high affinity, long plasma half‐life, safety, and analgesic efficacy of felinized anti‐NGF mAb (NV‐02) support further investigation of the analgesic potential of this antibody in the cat.
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spelling pubmed-50945432016-11-09 In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats Gearing, D.P. Huebner, M. Virtue, E.R. Knight, K. Hansen, P. Lascelles, B.D.X. Gearing, R.P. Drew, A.C. J Vet Intern Med SMALL ANIMAL BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This study describes the design and characterization of a fully felinized anti‐NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self‐resolving, acute inflammation model were investigated in cats. ANIMALS: Thirty‐eight cats at a research colony at Charles River Laboratories, Ireland. METHODS: Felinized anti‐NGF mAb, NV‐02, was produced using a complementary DNA (cDNA)‐based method (PETization). Purified NV‐02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin‐induced inflammatory pain. RESULTS: Anti‐NGF mAb, NV‐02 neutralized NGF with high affinity and potency and did not bind complement. NV‐02‐administered SC had a plasma half‐life of 7–15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV‐02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: The high affinity, long plasma half‐life, safety, and analgesic efficacy of felinized anti‐NGF mAb (NV‐02) support further investigation of the analgesic potential of this antibody in the cat. John Wiley and Sons Inc. 2016-06-15 2016 /pmc/articles/PMC5094543/ /pubmed/27306920 http://dx.doi.org/10.1111/jvim.13985 Text en Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle SMALL ANIMAL
Gearing, D.P.
Huebner, M.
Virtue, E.R.
Knight, K.
Hansen, P.
Lascelles, B.D.X.
Gearing, R.P.
Drew, A.C.
In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title_full In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title_fullStr In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title_full_unstemmed In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title_short In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
title_sort in vitro and in vivo characterization of a fully felinized therapeutic anti‐nerve growth factor monoclonal antibody for the treatment of pain in cats
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094543/
https://www.ncbi.nlm.nih.gov/pubmed/27306920
http://dx.doi.org/10.1111/jvim.13985
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