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

Abstract

Targeted therapy is a promising approach to improve the treatment of tumors, including ocular malignancies. Current therapies, such as radiotherapy and surgery, often lead to serious damage to vision or to loss of the eye. New approaches have examined nanoparticles for use as targeted delivery vehicles for drugs. A newly-developed virus-like drug conjugate is a promising nanoparticle with a defined target: the novel virus-like particle-photosensitizer conjugate Belzupacap sarotalocan (Bel-sar, previous name AU-011). Bel-sar is being used to treat small uveal melanoma or indeterminate choroidal pigmented lesions. This virus-like particle is derived from the capsid proteins of Human Papilloma Virus and specifically targets tumor cells that express cell surface heparan sulfate proteoglycans. Infrared laser is used to activate the conjugated phthalocyanine photosensitizer of the virus-like drug conjugate and a photochemical reaction known as photodynamic therapy is initiated. Photodynamic therapy is a minimally invasive treatment for specific types of cancer and has been used in the clinic for decades. In this review, we summarize the application of this novel light-activated virus-like particle conjugate in pre-clinical and clinical studies and discuss its potential to treat ocular malignancies, such as uveal melanoma and conjunctival melanoma. We furthermore discuss the combination with immunotherapy and its application on pigmented and non-pigmented tumors as well as its effect on macrophage polarization, which is important to achieve effective results in immunotherapy.