PT  - JOURNAL ARTICLE
AU  - David Kallenberg
AU  - Vineeta Tripathi
AU  - Faiza Javaid
AU  - Camilla Pilotti
AU  - Jestin George
AU  - Sterenn Davis
AU  - Jack WD Blackburn
AU  - Marie O’Connor
AU  - Laura Dowsett
AU  - Chantelle E Bowers
AU  - Sidath Liyanage
AU  - Morgane Gourlaouen
AU  - Alexandra Hoeh
AU  - Filipa Mota
AU  - David Selwood
AU  - James Bainbridge
AU  - Adnan Tufail
AU  - Vijay Chudasama
AU  - John Greenwood
AU  - Stephen E Moss
TI  - A Humanized Antibody against LRG1 that Inhibits Angiogenesis and Reduces Retinal Vascular Leakage
AID  - 10.1101/2020.07.25.218149
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.07.25.218149
4099  - http://biorxiv.org/content/early/2021/03/22/2020.07.25.218149.short
4100  - http://biorxiv.org/content/early/2021/03/22/2020.07.25.218149.full
AB  - Pathological angiogenesis contributes to morbidity in a number of diseases including cancer, diabetic retinopathy and the neovascular form of age-related macular degeneration, leading to significant efforts to develop effective anti-angiogenic therapeutics for these conditions. The field is dominated by inhibitors of vascular endothelial growth factor (VEGF), yet angiogenesis can also be driven and modified by other factors. We have previously demonstrated that leucine-rich alpha-2-glycoprotein 1 (LRG1) contributes to abnormal vessel growth by activating a TGFß switch. Here we report the development and characterisation of a function-blocking fully humanised IgG4 and its Fab fragment, that bind to LRG1 with high affinity and specificity and inhibit vascular leakage in the mouse model of laser-induced choroidal neovascularisation. In summary, we have developed a therapeutic antibody that targets a VEGF-independent signalling axis, which may be effective in a number of conditions either as monotherapy or in combination with other vascular targeted therapies.Competing Interest StatementS.E.M. and J.Gr. are founders of and shareholders in PanAngium Therapeutics that owns the commercialisation rights to Magacizumab and MagaFab. S.E.M., J.Gr. and V.T. are named inventors on patents relating to Magacizumab and MagaFab. V.C. is a Director of the spin-out ThioLogics, but there are no competing financial interests to declare.