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    Promising advances in uveal melanoma treatment

    Light-activated nanoparticles, immune therapy may be change clinical paradigm

     

    Basic research has yielded a good understanding of the pathway that leads a healthy melanocyte to mutate into melanoma. Dr. Shields and her colleagues are exploring a vaccine against one of these mutations, GNAQ. The vaccine has proved successful in mice and oncologists at Wills Eye are now preparing for trials in humans.

    Genetic studies have helped pinpoint which patients are most likely to develop metastatic disease. In the past, such prognoses depended on tumor size. Now, clinicians can use needle biopsies to look for chromosomal abnormalities.

    That technique has proved useful in therapy with sunitinib, an anti-VEGF agent used in kidney, pancreatic, and other cancers. Twenty percent of a group at high risk of metastases treated with sunitinib developed metastatic cancer, far less risk compared with 43% of a control group that developed metastatic cancer.

    A group from the Netherlands is working on adjuvant dendritic cell vaccination. In one study, 30% of patients with metastasis showed a response. In another study, patients who showed a favorable skin test response to the vaccine were less likely to develop metastatic disease when treated with the vaccine.

    In another immunotherapy approach, researchers infuse a “match-maker” drug that has receptors for both melanoma and T cell lymphocytes, thereby attracting the T cells to attack the melanoma. So far, Dr. Shields and her team at Thomas Jefferson University, Department of Medical Oncology, have treated 14 metastatic patients. The average survival in patients with this diagnosis is 4 to 5 months, but in a year only one of the patients treated this way has died.

    “So far, we’ve prolonged 13 lives with comfort,” Dr. Shields said.

    Taking a different tack, light-activated AU-011 (developed by Aura Biosciences), consists of nanoparticles that have only the capsid of human papilloma virus without the DNA and an attraction for heparin sulfate, which coats melanoma cells.

    The nanoparticles attach to melanoma cells and leave a chromophore tail sticking out. Clinicians can target this chromophore with a laser that disrupts the cancer cells. Studies in rabbits and dogs have proved successful, and the company hopes to begin clinical trials soon at several centers in the United States.

    “We’re so excited about this,” said Dr. Shields. “It could be a paradigm change in the way we manage small uveal melanoma.”

    In the future, patients with uveal melanoma may receive treatment that combines these approaches, both targeted treatment of the affected cells in the eyes and systemic immunotherapy to prevent metastasis, said Dr. Shields. “We are really pushing hard to develop a cure for melanoma,” she said.

    For now, in most cases the new treatments can only be administered as part of a trial, said Dr. Shields.

    “I generally ask our oncologists to see if the patient fits into any of their protocols,” she said. “If they qualify, it is a low cost for the patient. If not qualified, then we discuss treatment off protocol.”

     

    Carol Shields, MD

    E: carolshields@gmail.com

    This article was adapted from Dr. Shields' presentation at Retina Subspecialty Day preceeding the 2016 American Academy of Ophthalmology meeting. Dr. Shields serves on the scientific board of Aura Biosciences.

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