1. Academic Validation
  2. Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

  • Ann Rheum Dis. 2019 Sep;78(9):1260-1268. doi: 10.1136/annrheumdis-2019-215119.
Adi Mor 1 Michal Segal Salto 2 Avi Katav 1 Neta Barashi 1 Victoria Edelshtein 1 Mirko Manetti 3 Yair Levi 4 Jacob George 5 Marco Matucci-Cerinic 6
Affiliations

Affiliations

  • 1 R&D, ChemomAb Ltd, Tel Aviv, Israel.
  • 2 R&D, ChemomAb Ltd, Tel Aviv, Israel michal@chemomab.com.
  • 3 Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.
  • 4 Department of Internal Medicine E, Meir Medical Center, Kfar-Saba, Israel.
  • 5 Heart Center, Kaplan Medical Center, Rehovot, Israel.
  • 6 Department of Experimental and Clinical Medicine, University of Florence, Department of Geriatric Medicine, Division of Rheumatology and Scleroderma Unit, AOUC, Florence, Italy.
Abstract

Objectives: We aimed to assess the expression of the CCL24 chemokine in systemic sclerosis (SSc) and to evaluate the possible pathogenic implications of the CCL24/CCR3 axis using both in vitro and in vivo models. We further investigated the efficacy of an anti-CCL24 monoclonal antibody (mAb), CM-101, in inhibiting cell activation as well as dermal and pulmonary inflammation and fibrosis in experimental animal models.

Methods: We used ELISA and fluorescence immunohistochemistry to determine CCL24 levels in serum and CCL24/CCR3 expression in skin biopsies of SSc patients. Skin fibroblasts and endothelial cells treated with CCL24 or SSc serum with or without CM-101 were used to follow cell activation and differentiation. Prevention and treatment in vivo bleomycin (BLM)-induced models were used to evaluate experimental dermal and pulmonary fibrosis progression following treatment with the CM-101 mAb.

Results: CCL24 circulating levels were significantly elevated in SSc patients. CCL24/CCR3 expression was strongly increased in SSc skin. Blockade of CCL24 with CM-101 significantly reduced the activation of dermal fibroblasts and their transition to myofibroblasts induced by SSc serum. CM-101 was also able to significantly inhibit endothelial cell activation induced by CCL24. In BLM-induced experimental animal models, CM-101 profoundly inhibited both dermal and pulmonary fibrosis and inflammation.

Conclusions: CCL24 plays an important role in pathological processes of skin and lung inflammation and fibrosis. Inhibition of CCL24 by CM-101 mAb can be potentially beneficial for therapeutic use in SSc patients.

Keywords

chemokines; inflammation; pulmonary fibrosis; systemic sclerosis.

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