Researchers discover common chemotherapeutic agent reduces resistance to virus therapy in brain tumor patients
Moffitt Cancer Center researchers, in conjunction with colleagues at University of Calgary, have found that the common chemotherapeutic agent cyclophosphamide can help improve the success of oncolytic virus therapy in patients with malignant gliomas, a common type of brain tumor. Oncolytic virus therapy is an innovative therapeutic approach that uses viruses to target and kill cancer cells. The viruses can be modified to allow them to target specific cancer cells or to deliver therapy-modifying genes.
Preclinical studies of oncolytic virus therapy in malignant glioma are promising; however, a potential problem with this approach is that the body's own immune system can recognize the virus and clear the infection, resulting in reduced therapeutic effects. For this study, researchers used a mouse model with an intact immune system to mimic what would occur in humans to determine how the immune system clears the oncolytic virus. They found that the area surrounding malignant gliomas has a high number of immune cells called microglial cells and macrophages. Infection with an oncolytic virus causes a substantial influx of additional immune cells into the tumor environment. The tumor-resident macrophage cells and the recruited immune cells are instrumental in clearing the oncolytic virus, thereby inhibiting its therapeutic effects.
The researchers believe that blocking the resident and infiltrating immune cells in the brain may allow the oncolytic virus to kill the malignant glioma cells. To test this hypothesis, they treated mice with the oncolytic virus and the immunosuppressive drug cyclophosphamide. They discovered that this combination treatment significantly blocked the influx of immune cells and resulted in increased survival.
"To make sure we are getting the 'biggest bang for the buck,' we needed to understand how the body was fighting the virus in the brain tumor so we can dampen its response and maximize the chance of cure," said Peter A. Forsyth, M.D., chair of the Neuro-Oncology Department at Moffitt. "We hope to take this therapeutic combination to clinical trials within the next five years. We are very excited by this discovery. "
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F. J. Zemp, B. A. McKenzie, X. Lun, K. M. Reilly, G. McFadden, V. W. Yong, P. A. Forsyth. Cellular factors promoting resistance to effective treatment of glioma with oncolytic Myxoma virus. Cancer Research, Published Online October 21 2014. doi: 10.1158/0008-5472.CAN-14-0876