Summary: Researchers in Singapore have found that PRL3-zumab, a monoclonal antibody developed locally as a cancer therapy, shows strong potential as a new treatment for two leading causes of vision loss: wet age-related macular degeneration (AMD) and diabetic retinopathy. In pre-clinical models, intravenous administration of PRL3-zumab reduced abnormal blood vessel leakage by 86% compared with standard intravitreal injections, while avoiding the risks associated with direct eye injections.
These findings suggest a promising alternative for patients who do not respond adequately to existing therapies and for those who would benefit from avoiding monthly eye injections. Human clinical trials are slated to begin in late 2025, pending further regulatory steps, offering a hopeful advance for ophthalmic care.
Key facts
- PRL3-zumab, originally developed as an anti-cancer antibody, reduced abnormal ocular vascular leakage by 86% in pre-clinical eye disease studies.
- The antibody can be delivered intravenously rather than by intravitreal injection, which may reduce injection-related complications.
- Singapore’s Health Sciences Authority (HSA) approved the move to human trials on 16 June 2025, with clinical studies expected to begin by late 2025.
Source: A*STAR
Overview
A team from A*STAR’s Institute of Molecular and Cell Biology (IMCB) together with local biotech Intra-ImmuSG (IISG) report pre-clinical results in Nature Communications that point to PRL3-zumab as a potential anti-angiogenic therapy for neovascular eye diseases. The studies focus on two major causes of irreversible vision loss worldwide: wet AMD and diabetic retinopathy.
Why a new approach is needed
Current standard care for neovascular eye diseases often requires monthly intravitreal injections directly into the eye to block pathological blood vessel growth and leakage. These injections carry risks such as infection and lens damage, and a substantial proportion of patients—up to 45% in some studies—do not achieve sufficient responses. Those limitations have driven the search for alternative therapies that are safer, more convenient, and effective for a broader group of patients.
What the study showed
In animal models of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), researchers observed upregulation of endogenous PRL3 protein in diseased retinal tissues, implicating PRL3 in pathological angiogenesis. When an anti-PRL3 antibody was given intravenously in the CNV model, it produced a substantially greater reduction in vascular leakage than intravitreal injection—an average improvement of 86% reported in the pre-clinical work. Intravenous delivery also maintained therapeutic levels in the eye for longer periods and avoided direct injection into the globe.
Cell-based experiments showed that VEGF increases PRL3 expression in human retinal microvascular endothelial cells (HRMECs), and that overexpression of PRL3 promotes endothelial proliferation, migration and permeability via signaling pathways including ERK1/2, AKT, Paxillin and SRC. Conversely, VEGF-driven proliferation was absent in PRL3-knockout HRMECs, supporting PRL3’s role in disease-related angiogenesis.
Safety and clinical readiness
PRL3-zumab has already completed Phase II trials as an intravenous cancer immunotherapy and has demonstrated a favourable safety profile in those studies. That existing clinical safety data provides a valuable foundation as researchers seek approval to test the antibody in people with neovascular eye diseases. Singapore’s HSA granted approval on 16 June 2025, and investigators expect to begin human trials by late 2025.
Translational potential and collaborative science
The repurposing of a cancer drug for eye disease highlights how fundamental discoveries in one field can open opportunities in another. Professor Qi Zeng, who first identified the PRL3 protein in 1998 and serves as senior author on the study, reflected that the trajectory from cancer biology to ophthalmology underscores the broader impact of basic research. Associate Professor Xinyi Su highlighted the collaborative environment in Singapore—linking scientists, clinicians and industry partners—as a key factor enabling this translational effort.
About this research
Author: Owen Sia ([email protected])
Source: A*STAR
Contact: Owen Sia – A*STAR
Image credit: Neuroscience News
Original research: PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases by Qi Zeng et al., Nature Communications. DOI: 10.1038/s41467-025-59929-2. Open access.
Abstract summary
Neovascular eye diseases are a major cause of irreversible blindness. The study reports specific upregulation of PRL3 in diseased choroid–RPE in a CNV mouse model and in diseased retina in an OIR model, indicating PRL3’s involvement in pathological angiogenesis. Intravenous administration of an anti-PRL3 antibody showed superior efficacy in reducing vascular leakage compared with intravitreal delivery, attributed in part to the larger systemic dose achievable by IV infusion. Mechanistic studies link PRL3 to VEGF-driven endothelial proliferation, migration and permeability through multiple signaling pathways. Given PRL3-zumab’s established safety profile from ongoing Phase II cancer trials, these findings support repurposing the antibody for treating neovascular eye diseases and justify advancing to human clinical trials.