Amelioration of Collagen-Induced Arthritis in Rats by a Monoclonal Antibody against the Novel Epitope of Cysteine Protease from P. gingivalis

Abstract

Abstract Background: The use of biological diseases-modifying anti-rheumatic drugs (bDAMRD) including anti-tumor necrosis factor-α (TNF-α) has revolutionized the therapy of rheumatoid arthritis (RA). However, approximately 30–40% of patients with RA do not response to anti-TNF therapy when used as the first-line bDMARD. Objective: The aim of the study is to develop a new, novel monoclonal antibody for the therapy of RA. Methods: Monoclonal antibody development: BALB/c mice were immunized with OVA-conjugated peptide for CIA. Spleen cells were collected for fusion with myeloma cells. The rats were divided into 6 groups: Normal control, CIA, IgG1(15 mg/kg)-treated CIA, low-mAb (3 mg/kg)-treated CIA, High-mAb (9 mg/kg)-treated CIA, and Enbrel (4.5 mg/kg)-treated CIA. Results: The monoclonal is only reacted to the immunized peptide and is IgG1 Kappa, high melting temperature with Tm=4.8, High binding to FCγRIIb and FCγR III, and low dissociation constant (Kd=19.6×10 −9) of Ag-mAb affinity. The mAb stains mainly on cytoplasm with several coarse discrete dots on SW982 cells. After treatment with this mAb in CIA, the mice have showed dose-dependent effects, improving articular index and ankle circumference, reduced inflammation and synovium proliferation, restored joint space narrowing, and cartilage on immunohistochemistry. The therapeutic results in the mAb-treated group has shown to be excellent in CIA animal RA model. Conclusion: We’ve generated a novel monoclonal antibody which has excellent therapeutic effects in the therapy of RA animal model. This study is the first time to demonstrate that targeting on the different signal pathway of CIA can have a promising effect on RA therapy.