Targeting ocular malignancy using a novel light-activated virus-like drug conjugate

Abstract

The aim of my the research is to develop a novel treatment strategy for ocular malignancies that preserves vision and the eye, while preventing metastases. This involves using a novel of photodynamic therapy (PDT). The core of this research is a virus-like particle-photosensitizer conjugate, known as Bel-sar (formerly AU-011), which is currently being tested in clinical trials for treating small choroidal melanomas or indeterminate pigmented lesions in the eye. In the thesis, we investigated the anti-tumor efficacy of Bel-sar in ocular malignancies with varying genetic profiles and levels of pigmentation. The findings demonstrate that Bel-sar effectively targets tumors, enhances drug accumulation within the tumor, and reduces off-target effects. Importantly, this therapy also proved effective in treating pigmented tumors, which are often more challenging due to their protective pigmentation. Our research further highlights the ability of Bel-sar PDT to induce immunogenic cell death. This process involves the exposure of damage-associated molecular patterns (DAMPs), which can trigger both local and systemic immune responses. The combination of Bel-sar PDT with immunotherapy has shown improved therapeutic outcomes compared to current treatments in preclinical models. This innovative therapy offers a promising new option for patients with choroidal and conjunctival melanomas. By advancing the understanding and application of photodynamic therapy, the research contributes to the development of more effective and less invasive cancer treatments.