Format

Send to

Choose Destination
Sci Rep. 2018 Feb 16;8(1):3212. doi: 10.1038/s41598-018-20811-5.

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis.

Author information

1
AdAlta Limited, La Trobe University, 15/2 Park Drive, Bundoora, 3083, Australia.
2
The Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Melbourne, 3086, Australia.
3
Cedars-Sinai, Medical Centre, Los Angeles, CA, 90048, USA.
4
Department of Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, 3000, Australia.
5
XL-protein GmbH, Lise-Meitner-Str. 30, 85354, Freising, Germany.
6
AdAlta Limited, La Trobe University, 15/2 Park Drive, Bundoora, 3083, Australia. M.Foley@latrobe.edu.au.
7
The Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Melbourne, 3086, Australia. M.Foley@latrobe.edu.au.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4+ fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue. We have engineered a novel fully human single domain antibody "i-body" called AD-114 that binds with high affinity to human CXCR4. We demonstrate here that AD-114 inhibits invasive wound healing and collagen 1 secretion by human IPF fibroblasts but not non-diseased control lung fibroblasts. Furthermore, in a murine bleomycin model of pulmonary fibrosis, AD-114 reduced the accumulation of fibrocytes (CXCR4+/Col1+/CD45+) in fibrotic murine lungs and ameliorated the degree of lung injury. Collectively, these studies demonstrate that AD-114 holds promise as a new biological therapeutic for the treatment of IPF.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center