Light-activated AU-011 has the potential to be the first targeted therapy ever developed for the primary treatment of ocular melanoma, the most common primary cancer of the eye, said Amy C. Schefler, MD, with Retina Consultants of Houston.
People diagnosed with ocular melanoma confront “an array of poor treatment options, which often result in severe vision loss, removal of the eye, and in about half of all cases, metastasis to the liver, where the disease is nearly always fatal,” according to Aura Biosciences, which developed this light-activated technology.
AU-011 is a first-in-class targeted therapy, a novel protein capsid-dye conjugate recombinantly derived from the capsid proteins of the papilloma virus; the FDA has already granted Fast Track Designation and Orphan Drug Designation, recognizing that there are no FDA-approved therapies and that the disease is serious and life-threatening, Dr. Schefler said.
The mechanism of action of AU-011 is targeted acute tumor cellular necrosis upon light activation. The capsid conjugates are delivered by intravitreal injection and selectively target the tumor cells in the choroid sparing the retina and other key ocular structures. This unique selectivity is due to the binding of the capsid conjugates to modified heparan sulfate proteoglycans (HSPGs) that are expressed on the tumor cell surface. The capsid protein is conjugated with a potent phthalocyanine photosensitizer, IRDye 700DX, that exerts its tumor cytotoxic effect through light-activation with a near-infrared 689-nm laser.
The mechanism of action has a dual selectivity. First, the capsid conjugates bind tumor cells selectively without binding other key eye structures and second, the laser beam activates the conjugated dye exclusively within the tumor generating potent cytotoxic oxygen free radical species that disrupt the tumor cell membrane, leading to targeted and acute tumor cellular necrosis, Dr. Schefler said.