PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases

Koon Hwee Ang, Min Thura, Queenie Shu Woon Tan, Abhishek Gupta, Kam Yew Kuan, Jie Li, Pei Ling Chia, Beiying Qiu, Jimmy Ming Hong, Ke Guo, Xiaomeng Wang, Xinyi Su and Qi Zeng ()
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Koon Hwee Ang: Technology and Research (A*STAR)
Min Thura: Technology and Research (A*STAR)
Queenie Shu Woon Tan: Technology and Research (A*STAR)
Abhishek Gupta: Technology and Research (A*STAR)
Kam Yew Kuan: Technology and Research (A*STAR)
Jie Li: Technology and Research (A*STAR)
Pei Ling Chia: Technology and Research (A*STAR)
Beiying Qiu: 8 College Road
Jimmy Ming Hong: Level 6 Discovery Tower
Ke Guo: Technology and Research (A*STAR)
Xiaomeng Wang: Technology and Research (A*STAR)
Xinyi Su: Technology and Research (A*STAR)
Qi Zeng: Technology and Research (A*STAR)

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Neovascular eye diseases represent a major cause of irreversible blindness. Here, we report the specific upregulation of endogenous PRL3 protein in diseased choroid-RPE in choroidal neovascularization (CNV) mouse model (male), and diseased retina in oxygen-induced retinopathy (OIR) mouse model (mixed gender), indicating PRL3’s role in neovascularization. Intravenous (IV) delivery of anti-PRL3 antibody in CNV model demonstrates superior efficacy in reducing vascular leakage compared to intravitreal (IVT) route due to larger dose permitted by IV. VEGF treatment upregulates endogenous PRL3 protein in human retinal microvascular endothelial cells (HRMECs). Retroviral PRL3 overexpression in HRMECs promotes endothelial proliferation, migration and permeability by facilitating the phosphorylation of ERK1/2, AKT, Paxillin and SRC. However, VEGF-induced proliferation is absent in PRL3-knockout HRMECs. PRL3-zumab, an anti-PRL3 humanized monoclonal antibody, has shown a strong safety profile in ongoing multi-national Phase II trials as an intravenous-administered cancer immunotherapeutic. PRL3’s involvement in ocular pathological angiogenesis suggests the potential of repurposing PRL3-zumab to treat neovascular eye diseases.

Date: 2025
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DOI: 10.1038/s41467-025-59929-2

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