Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Medical and patient unmet needs still existed in rheumatoid arthritis (RA) global market due to the side effects treated for long duration and sometimes non-response to existing medicines. We developed a novel synthetic peptide, KINE-101 with distinct mode of action to activate the regulatory T (Treg) cells.
Methods: The efficacy of KINE-101 was investigated by collagen-induced arthritis (CIA) mouse model. The activity and differentiation of Treg cells by KINE-101 were determined by FACS analysis using various Treg cells markers. Treg cells depletion study was evaluated using CD25 antibody. Autoantibody production was measured by ELISA and germinal center B cells were stained with B cells markers. Osteoclastogenesis was assessed Safranin O staining using joint tissue section. Preliminary toxicology study was accomplished to confirm the safety of KINE-101.
Results: In CIA model, KINE-101 showed similar efficacy in controlling arthritis index compared to MTX. Surprisingly, activation and differentiation of Treg cells were significantly increased by treatment of KINE-101. The effect of KINE-101 mediated by Treg cells was confirmed by Treg cell depletion study in CIA mouse model. Moreover, collagen type II specific autoantibody production were dramatically decreased and germinal center B cells were inactivated by treatment of KINE-101. Safranin-O staining results show KINE-101 suppresses cartilage damage through inhibiting osteoclastogenesis. No significant toxicological findings were observed as a result of preliminary toxicology study.
Conclusion: We developed a novel synthetic peptide, KINE-101, for the treatment of rheumatoid arthritis. KINE-101 shows high remission of RA symptoms in CIA model by activating Treg cells resulting in reduction of autoantibody production. These results suggest that KINE-101 may serve as a first-in-class therapeutic to control autoimmune diseases with Treg cells regulation.
To cite this abstract in AMA style:Kim M, Lee S, Roh J, Kwon J, Park S, Cho D. KINE-101, a Novel Synthetic Peptide with Potent Regulatory T Cells Activation to Treat Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/kine-101-a-novel-synthetic-peptide-with-potent-regulatory-t-cells-activation-to-treat-rheumatoid-arthritis/. Accessed January 27, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/kine-101-a-novel-synthetic-peptide-with-potent-regulatory-t-cells-activation-to-treat-rheumatoid-arthritis/