"Eradicating cancer without damaging healthy tissue is the Holy Grail of cancer researchers. Wills Eye Hospital in Philadelphia is testing a novel lightactivated drug designed to do just that in the eye raising hopes for the first ocular melanoma treatment that would preserve patients vision. Sparing eyesight could encourage earlier detection and treatment thus reducing the chance of metastases  the deadly spread that killed acclaimed author and neurologist Oliver Sacks in . A close up of the ophthalmic laser used to activate Aura Biosciences experimental drug. This could be a gamechanger if it works said Carol Shields an ocular oncologist at Wills Eye and Thomas Jefferson University. Thats still a big if. Shields treated the first patient a yearold man from Hazleton Pa. in March. A dozen patients in all will be treated at Wills and five other centers over the next two years  and thats just the first of three clinical trials needed to win approval from the U.S. Food and Drug Administration. But if Aura Biosciences experimental therapy vanquishes the rare eye malignancy it could pave the way for a new class of exquisitely precise cancer therapies. In lab experiments the drugs artificial viral nanoparticles  derived from groundbreaking technology pioneered at the National Cancer Institute  have been shown to zero in on and bind to many types of malignant cells without harming normal cells. We decided to first focus on a cancer with medical need and no other drug option Auras founding CEO Elisabet de los Pinos said of ocular melanoma. But we think that our technology can be applied to other cancers including bladder and head and neck. A freckle in the eye Many people have a harmless freckle or nevus in their eyes formed by the same pigmentcarrying melanocytes that produce freckles in the skin. Just as in the skin the eye spots can turn malignant. Sun exposure is not clearly linked to ocular melanoma but fair skin and light eye color are risk factors. Carol shields When a benign freckle in the eye turns malignant it grows into an ocular melanoma a rare but potentially lifethreatening cancer. While the disease is rare with about  new diagnoses and  deaths in the United States each year it often goes undiagnosed until it affects vision. Sacks   known for books including Awakenings and The Minds Eye in which he tells the story of his own cancer  said his symptoms hit suddenly wiping out a triangular chunk of the vision in his right eye. Sacks decided to have a chip of radioactive iodine embedded in his eye to treat the tumor. It caused severe pain hallucinations and vision loss in the center of that eye. The radiation and later lasering ultimately left that eye blind. Carol shields The dark spot in the upper center region is a benign freckle formed by pigmented cells called melanocytes. Other ocular melanoma treatments including proton beams gamma knife and surgery to cut out the tumor also have damaging side effects. If these fail to control the cancer the eye must be removed. The first patient Ed Tuggle a maintenance supervisor for a food company never had symptoms. In  his ophthalmologist spotted a tiny freckle during a routine eye exam. Last year the same doctor saw that the lesion had grown. Although it was still small  about onetenth of an inch  he sent Tuggle to Wills where Shields did a battery of tests and concluded that it was malignant. Patients with small tumors such as Tuggles often choose monitoring rather than immediate visiondamaging treatment. But holding off can be anxietyprovoking given that studies indicate up to  percent of ocular melanomas metastasize. When Shields proposed another option  Auras clinical trial  Tuggle and his wife Daneen a nurse were eager. The actual procedure in early March was a breeze Tuggle recalled. Shields numbed his eye injected the drug and six hours later used a laser to activate the lightsensitive dye that is part of the therapy. His dose was purposely low intended more to test safety than effectiveness. Patients in the next trial will get multiple higher doses. Still a month after Tuggles injection Shields was pleased to find that the tumor had begun to atrophy. Based on animal studies it takes three or four months to gauge the response. Ive got a lot of faith said Tuggle who said he has had no side effects. In my mind its already worked. Wills Eye Hospital ocular oncologist Carol Shields puts a  protective lens on patient Ed Tuggles eye in preparation for a laser treatment. The laser activates an experimental targeted cancer drug previously injected in his eye. A new way to target tumors De los Pinos a molecular biologist who previously worked in Eli Lilly  Co.s oncology division founded Cambridge Mass.based Aura in  with the goal of developing a highly targeted approach to cancer treatment. The first product candidate is built on decades of advances involving of all things the human wart virus   human papillomavirus or HPV. In the s certain virulent strains of HPV were shown to cause cervical cancer. In the s scientists figured out how to make harmless empty HPV shells  called viruslike particles  to prime the immune system to ward off the real germ. Viruslike particles became the basis of Mercks groundbreaking cervical cancer prevention vaccine Gardasil approved in . More recently a team at the National Cancer Institute led by John T. Schiller and Douglas R. Lowy deciphered how HPV infects certain cervical cells in the first place. Physically disrupted cells overproduce a carbohydrate molecule that normally helps with wound healing. The virus binds to that molecule called heparan sulfate proteoglycans. Healthy intact cells meanwhile resist being bound. Using animal models the NCI researchers showed that viruslike particles behaved like the actual virus using the carbohydrate to attach to tumors. And not just in the cervix. In  Schiller Lowy Auras de los Pinos and others published a study that showed viruslike particles  can infect a broad range of cancer cell types  including ovarian and lung by binding to the carbohydrate. Since viruslike particles are harmless on their own Auras are coupled with a lightsensitive dye. When activated by laser light the dye becomes toxic to the tumor cells membranes and  if all goes as expected  selectively kills the cancer. Although ocular melanoma is rare Shields has long urged people to get annual eye checks because finding it early is critical. Now she foresees a way to make early detection less dreadful. Were hoping this becomes a new alternative in the management of melanoma of the eye she said."