In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
2016
Gearing, D.P. | Huebner, M. | Virtue, E.R. | Knight, K. | Hansen, P. | Lascelles, B.D.X. | Gearing, R.P. | Drew, A.C.
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.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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