Combination therapy a one-two punch to KO aggressive brain cancer

A new study has found that combining radiotherapy with a cancer-targeting virus was more effective at combatting a hard-to-treat, deadly form of brain tumor than using either therapy alone.

According to the National Brain Tumor Society, glioblastoma (GB) accounts for just over half – 50.1% – of all primary malignant brain tumors. It’s one of the most deadly, treatment-resistant cancers. The survival rate for GB is only 6.9%, and the average length of survival for people diagnosed with this type of cancer is just eight months.

Because of GB’s aggressiveness, its treatment needs to be equally aggressive. Radiotherapy is the front-line treatment, especially when the tumor is inoperable, but has a tendency to miss invasive cancer cells. Oncolytic virus (OV) therapy has emerged as a class of immunotherapy that uses viruses to infect and kill cancer cells while simultaneously stimulating an anti-tumor response in the immune system. The vaccinia virus (VACV) is one such oncolytic. VACV is a large, double-stranded DNA virus used to vaccinate against smallpox that has been found to have anti-tumor properties.

A new study by researchers at the University of Alberta, Canada, examined the effectiveness of combining radiotherapy and OV therapy in treating GB.

“There aren’t many therapies for cancer that work really well on their own because the nature of tumors is that they are not uniform due to high mutation rates, so combinations of therapies have the greatest chance of success,” said Mary Hitt, corresponding author of the study.

They treated mice with GB tumors simultaneously with high-dose radiation and a genetically engineered type of VACV, in addition to evaluating the effectiveness of using each treatment alone. The researchers found that the mice receiving both treatments had considerably better therapeutic outcomes than those receiving only one.

Mice that’d received radiation alone saw a 20% tumor clearance (cure) rate, and the cure rate for the mice receiving only VACV was 15%. However, 67% of mice treated with both therapies were cleared of their GM tumors. Moreover, when the researchers reintroduced fresh cancer cells to some cured mice, 62% of the combination-treatment animals rejected or resisted new cancer growth.

“It was quite remarkable to see the effect of the combination was greater than either of its parts alone,” said Quinn Storozynsky, the study’s lead author.

The researchers say their findings suggest that combination therapy is effective for coopting the body’s immune system to help fight the immune suppression that occurs with GB.

“You need some way to seek and destroy cancer cells, so if you can harness the immune system, that’s an incredible way to have this evolutionarily conserved response do the work for you,” said Storozynsky.

The researchers would like to see further studies using VACV or other OV therapies in combination with different doses of radiation to optimize the treatment’s effect. Or to test the effectiveness of using another immunotherapeutic agent known as an immune checkpoint inhibitor, which evokes an anti-tumor reaction in the body’s immune cells.

Currently, in the US, the FDA has approved only one OV therapy, a modified herpes simplex virus (HSV), for use in some patients with melanoma. Three other oncolytic viruses have been approved in one or a few other countries. The researchers hope that more OV therapies will be approved but understand that it will take time.

“It’s a slow process of confirming the safety and effectiveness through clinical trials, but I think it’s just a matter of time,” Hitt said.

The study was published in the journal Cancer Letters.

Source: University of Alberta

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