A Humanized Antibody against LRG1 that Inhibits Angiogenesis and Reduces Retinal Vascular Leakage
Kallenberg, D.; Tripathi, V.; Javaid, F.; Pilotti, C.; George, J.; Davis, S.; Blackburn, J. W.; O'Connor, M.; Dowsett, L.; Bowers, C.; Liyanage, S. E.; Gourlaouen, M.; Hoeh, A.; Mota, F.; Selwood, D.; Bainbridge, J.; Chudasama, V.; Greenwood, J.; Moss, S. E.
Show abstract
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 TGF{beta} 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.
Matching journals
The top 13 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD 93%
- Restoring AIBP expression in the retina provides neuroprotection in glaucoma 91%
- Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy 91%
Similar papers in this journal
- Transmembrane Stem Cell Factor Protein Therapeutics EnhanceRevascularization in Ischemia without Mast Cell Activation 93%
- IOP-induced blood-retinal barrier compromise contributes to RGC death in glaucoma 92%
- Cellular-level phenotyping of tumor-immune microenvironment (TiME) in patients in vivo reveals distinct inflammation and endothelial anergy signatures 92%
Similar papers in this journal
- Antithrombotic Efficacy and Bleeding Risks of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments 90%
- Temporal in vivo platelet labelling in mice reveals age-dependent receptor expression and conservation of specific mRNAs 89%
- The unconventional Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane 89%
Similar papers in this journal
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology 93%
- C1q limits cystoid edema by maintaining basal beta-catenin-dependent signaling and blood-retina barrier function 93%
- IL-23 drives uveitis by acting on a novel population of tissue-resident entheseal T cells 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.