Chemotherapy Drug Reduces Resistance to Brain Tumor Therapy

Cyclophosphamide found to improve the success of virus therapy in patients with malignant gliomas.

A common chemotherapy drug has been found to improve the success of oncolytic virus therapy in the treatment of brain tumors, according to the results of a recent study.

Published in the October 21, 2014 online edition of Cancer Research, researchers found the chemotherapeutic agent cyclophosphamide helps to enhance the success of oncolytic virus therapy in patients with malignant gliomas. Oncolytic virus therapy, which utilizes viruses to eliminate specific cancer cells, can also be modified to deliver therapy-modifying genes.

A potential issue with the therapy uncovered in prior studies involved the body's immune system recognizing and clearing the virus therapy, which reduces the treatment’s therapeutic effects. For the current study, researchers utilized a mouse model with an intact immune system, to imitate the process that would occur in humans, in order to evaluate how oncolytic viruses are cleared by the immune system.

The researchers determined the region that surrounds malignant gliomas carry a high number of immune cells. As a result, oncolytic virus infection leads to a substantial increase of immune cells into the tumor environment.

The tumor’s macrophage cells and the recruited immune cells are crucial to the process of clearing the oncolytic virus, which inhibits the therapeutic effects.

By blocking the resident and infiltrating immune cells in the brain, the study found that the oncolytic virus may be enabled to kill the malignant glioma cells. The researchers subsequently treated mice with the oncolytic virus and cyclophosphamide.

The combination treatment was discovered to significantly block the influx of immune cells, which 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," Peter A. Forsyth, MD, chair of the Neuro-Oncology Department at Moffitt Cancer Center, said in a press release. "We hope to take this therapeutic combination to clinical trials within the next 5 years. We are very excited by this discovery. "