Immunome Research
Open Access

i-bodies: Novel single domain antibodies against GPCRs and Ion channels in the treatment of fibrosis

2^nd International Conference on Antibodies and Therapeutics

July 11-12, 2016 Philadelphia, USA

Michael Foley

La Trobe University, Australia

Posters & Accepted Abstracts: Immunome Res

Abstract :

i-bodies are small, stable, human scaffolds engineered from information gained from the shark single domain antibodies. The presence of a long CDR3 enables better access to complex proteins such as GPCRs and ion channels. We have screened this phage displayed i-body library on GPCRs and ion channels expressed in different formats. We have obtained a panel of high affinity single domain antibodies specific for the chemokine receptor CXCR4. CXCR4 is known to be up-regulated in a number of cancers and recently has been implicated as a central player and a therapeutic target in fibrosis. Although all i-bodies bind with high affinity each of i-bodies have different functional profiles with respect to modulation of cAMP, calcium efflux, inhibition of �?�?�?�?�?�?�?²-arrestin signaling and blocking of HIV infection. When two lead i-bodies were injected intraperitoneally they were found to completely block SDF-1- induced leukocyte recruitment in an air pouch model of inflammation in mice. Importantly, unlike most other CXCR4 antagonists, they did not mobilize stem cells from the bone marrow. Thus these i-bodies would be ideal for long-term anti-fibrosis therapy. Indeed we have shown that i-bodies are able to block the recruitment of fibrocytes into the lungs of mice with bleomycin induced pulmonary fibrosis and that the anti CXCR4 i-bodies have anti-inflammatory and anti fibrotic effects in several different animal models. Moreover we suggest that i-body provide a unique resource for obtaining human antibody single domains to currently intractable membrane proteins.

Biography :

Email: m.foley@latrobe.edu.au