New laser treatment for neovascular AMD targeting VEGFR2 with near-infrared photoimmunotherapy

Abstract

Purpose : Age-related macular degeneration (AMD) remains a leading cause of vision impairment and blindness among the elderly, and its prevalence continues to rise with the aging population. Current AMD treatments have limited effectiveness, emphasizing the need for innovative therapies.
Photoimmunotherapy (PIT), which has shown success in cancer treatment, offers a promising solution. In PIT, photosensitive antibodies are attached to cells expressing specific antigens, and upon exposure to near-infrared (NIR) light, the antibodies are activated, inducing targeted cell death while preserving healthy tissues.
The purpose of this study is to validate the effectiveness and impact of using photosensitive antibodies targeting neovascularization for PIT as a novel treatment for AMD. This will be achieved through animal model experiments aimed at the removal of choroidal neovascularization (CNV).

Methods : CNV model mice were generated by laser irradiation of the fundus of 7-week-old C57BL/6J mice. 6 days after laser irradiation, Alexa 488-conjugated anti-VEGFR2 antibody was administered systemically, and the localization of the anti-VEGFR2 antibody at 24 hours after administration was confirmed. Next, 6 days after CNV induction, the antibody-IR700 complex, in which the anti-VEGFR2 antibody was conjugated to the photosensitive substance IR700, was administered systemically, and NIR-PIT was performed by irradiating the retina with near-infrared light at 24 hours after antibody administration. 3 days after NIR-PIT, isolectin IB4 staining on the retinal flat mount was performed to measure the volume of CNV.

Results : After 24 hours following administration, the presence of the antibody-Alexa488 complex was confirmed within the area of CNV. This suggests the localization of the antibody-photosensitizer complex at the core of laser-induced CNV. 3 days after NIR-PIT, a significant reduction in CNV volume was observed in the group receiving the antibody-IR700 complex.

Conclusions : This study has revealed that the utilization of PIT with the anti-VEGFR2 antibody-IR700 complex effectively reduces laser-induced CNV. These findings provide a promising avenue for the new AMD treatment, addressing the current limitations in AMD therapy.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.