改良麻疹病毒可能治愈小儿脑瘤

The use of modified measles¹（麻疹） virus may represent a new treatment for a childhood brain tumor² known as medulloblastoma（成神经管细胞瘤） , according to a new study appearing in Neuro-Oncology. Medulloblastoma is the most common malignant³（恶性的） central nervous system tumor of childhood, accounting⁴ for about 20 percent of pediatric（小儿科的） brain tumors. These tumors are located in the cerebellum（小脑） , the area of the brain that controls balance and other complex motor functions. Refinements⁵ in treatment have increased the 5-year survival to close to 70 percent, but treatment still involves invasive surgery, radiation therapy and chemotherapy（化学疗法） .

"There is still an urgent need to investigate alternative therapeutic⁶ approaches that are more effective and have less toxic⁷ side effects," said study lead author Corey Raffel, MD, PhD, chief of Neurosurgery at Nationwide Children's Hospital and a faculty⁸ member of The Ohio State University College of Medicine.

Vaccine⁹ strains of measles virus have been used to kill tumor cells in a number of tumor types including one type of adult brain tumor. One vaccine strain of measles, the Edmonston strain, targets the cell surface receptor CD46 to gain entry into susceptible¹⁰ cells. "This preference most likely explains the efficacy of Edmonston strains in killing¹¹ tumor cells, given the high level of expression of CD46 in multiple tumor types," said Dr. Raffel. "It is also the reason we chose to explore a modified Edmonston's strain of measles virus for use in medulloblastoma."

The team's laboratory studies revealed that established medulloblastoma cell lines express the measles receptor, CD46 and that medulloblastoma specimens¹² removed from patients have a high level of CD46 expression.

"Other oncolytic（溶瘤细胞的） viruses have been explored as possible treatment modalities（样式，形态） for medulloblastoma," said Dr. Raffel. "The fact that all of the surgical¹³ medulloblastoma specimens that we examined expressed the measles virus receptor leads us to believe that measles virus may have some advantages over other viruses."

Having demonstrated receptor expression, the team treated the medulloblastoma cell lines with the modified measles virus. Within 72 hours, all cell lines exhibited significant tumor cell death.

The team also administered the modified measles virus to mouse models of medulloblastoma, administering treatment every other day for 10 days. By the end of the study period, pathological（病理学的） review of the animals confirmed that two of the animals were free of tumor and the third had a very small amount of residual¹⁴（剩余的，残留的） tumor. In eight of the eleven mice the primary tumor was eradicated¹⁵（摆脱，擦掉） .

"Our study demonstrates that a modified measles virus has therapeutic potential in the treatment of intracerebral（大脑内的） medulloblastoma," said Dr. Raffel. "These results provide initial data to be pursued with additional studies toward the goal of using the virus in a clinical trial for the treatment of medulloblastoma. Measles virus therapy could be applied¹⁷ to the tumor bed following surgical resection（切除术） to target microscopic¹⁸（微观的） residual disease. This approach could potentially alleviate¹⁹ the need for radiation and chemotherapy."

The data also suggest that the measles virus may be a potential therapy for tumors that have spread to the cerebral¹⁶（大脑的） spinal²⁰ fluid. "When tumor cells gain access to the cerebral spinal fluid and the subarachnoid space（蛛网膜下腔） , current therapy is largely ineffective," said Dr. Raffel. We have preliminary data in the lab demonstrating efficacy of measles virus in treating disseminated²¹（散播性的） tumor in a mouse model of CSF disease.

Researchers now plan to investigate the optimal²² dose schedule for injection of the virus. They also intend to examine how modifications²³ of the virus might lead to more effective treatment of the tumor. "Overall, the results suggest that use of modified measles virus may represent a new treatment for medulloblastoma," said Dr. Raffel.