Is Oncolytic Virotherapy Combination the Answer to Pediatric Cancer Treatment?

Combining oncolytic virotherapy with PD-1 blockades shows promise treating rhabdomyosarcoma.

Oncolytic virotherapy is an emerging treatment that uses replicated viruses to target and kill cancer cells.

In a study published in Scientific Reports, investigators combined virotherapy with programmed cell death protein (PD-1) blockades to treat a mouse model of rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a type of cancer comprised of cells that normally develop into skeletal muscles. Most diagnoses occur in children and teens, with more than half in children younger than 10 years, according to the American Cancer Society.

During the study, the investigators used oncolytic virotherapy and blocked the signaling of PD-1 proteins—–which mediates the suppression of T cells. These oncolytic viruses can infect and kill malignant cells, while leaving normal cells untouched.

“Other researchers have recognized that if we can block the PD-1 checkpoint and unleash the T cells a bit more, they might fight cancer better,” said senior author Timothy Cripe, MD, PhD. “We thought that if a virus infection brings in more T cells, and the PD-1 blockade allows those cells to fight cancer cells, then maybe the 2 therapies will work better together.”

The results of the study showed that the immunotherapy combination slowed tumor growth and enhanced overall survival in the mouse model of rhabdomyosarcoma.

“We used a mouse model to demonstrate that when we combine oncolytic therapy with PD-1 blockade, we see a better therapeutic outcome compared to either of the therapies individually,” said first author Chun-Yu Chen, PhD.

The combination is successful because it requires more T cells that attack infections and tumors without increasing regulatory T cells that suppress an immune response, the authors noted.

Currently, the investigators are working with a company to determine whether they will move forward with clinical trials. Oncolytic virotherapy and PD-1 blockades are FDA-approved to treat cancer, and the latest findings provides preclinical data to support use of the combination in pediatric cancer patients, according to the authors.

The investigators also hope to examine how differences in immunogenicity may affect the success of the combination immunotherapy.

“Our paper gives us some clues as to predictive biomarkers of who might respond best to this type of treatment,” Dr Cripe said. “If we can identify patients who have a tumor that is recognized by the immune system better, we can individually select patients in which this combination treatment will work best.

“It has been shown that immunotherapy works for some adult cancers; the question is, what impact will it have on childhood cancers? We are fortunate to be at an institution that has all the resources that allow us to study this in the lab and in the clinical setting and find out its full potential.”