Curing the childhood eye cancer retinoblastoma often comes at a cost. The tumor, which sprouts in the retina and primarily occurs in children under the age of 5, is fatal if not treated. Yet chemotherapy can cause permanent vision loss, and patients sometimes need surgery to remove one or both eyes. Now, scientists have found that a cancer-slaying virus seems to combat this cancer in mice without serious side effects. A clinical trial has also shown early signs of promise.
“It’s potentially a game-changer,” says ophthalmic oncologist David Abramson of Memorial Sloan Kettering Cancer Center in New York City, who wasn’t connected to the study.
Researchers have tested cancer-targeting viruses in other types of tumors, but no one had pitted them against retinoblastoma. The tumors grow when there are defects in a molecular pathway that keeps cells from dividing out of control. Oncology researcher Ángel Montero Carcaboso of the Sant Joan de Déu Research Institute in Barcelona, Spain, and colleagues used a type of virus known as adenovirus that typically causes only mild respiratory infections in people. It had been genetically modified so it was missing a key gene and could only reproduce inside cells in which the retinoblastoma pathway had malfunctioned.
To determine whether such a virus would be safe, the scientists injected it into the eyes of rabbits without the tumor. The virus triggered side effects such as inflammation and fluid buildup in the eyes, but they disappeared within 6 weeks. Moreover, little of the virus escaped from the eyes, and it didn’t appear to reproduce elsewhere in the animals’ bodies, suggesting it wouldn’t cause harm in other organs.
Next, the researchers injected the virus into the eyes of mice with the eye cancer. They gauged its effectiveness by measuring the amount of time required for the cancer to damage an animal’s eye so badly it had to be removed. The rodents’ eyes remained intact roughly twice as long if they received the virus than if they received no treatment. Eye “survival” was also more than twice as long in animals injected with the highest dose of the virus than in mice treated with two types of chemotherapy, the team reports online today in Science Translational Medicine.
On the strength of those results, Carcaboso and colleagues have begun a clinical trial to test whether the virus is safe in children with retinoblastomas that haven’t responded to chemotherapy or radiation treatment. Two patients have received the virus so far.
The researchers have noted preliminary signs that the virus is targeting the tumors. That discovery was an upside of an unfortunate outcome for one child, whose eye had to be removed because its interior became too cloudy to monitor the tumor. An analysis of the eye showed the virus was reproducing in some tumor cells. The scientists uncovered no evidence that the virus was growing in normal eye cells or damaging the retina.
In the second patient, the virus appeared to be shrinking and destroying tumor fragments floating within the eye. These shards, known as vitreous seeds, are dangerous because they can settle on the retina and grow into new tumors, but they are hard to eliminate with chemotherapy. Carcaboso says the researchers plan to enroll more children in the study and further test the virus’s safety and capabilities.
“It is exciting that this virus targets molecular signatures of tumor cells, while apparently leaving normal ocular structures undamaged,” says ocular oncologist Anthony Daniels of Vanderbilt University Medical Center in Nashville, who was not involved with the work. “Whether this approach can achieve a durable cure remains to be seen.”
Neurosurgeon E. Antonio Chiocca of Harvard Medical School and Brigham and Women’s Hospital in Boston, who has tested cancer-targeting viruses as a treatment for brain cancer, agrees that the results are promising. However, he cautions, “We don’t know enough to say whether this will be a therapy.” For example, the authors need to nail down the response of the immune system, he says, which could help destroy the tumor or turn against the viruses and “kill your therapy.”
Source: Science Magazine