According to a recent study, published in the Molecular Therapy–Oncolytics journal, viral therapy for childhood cancer could improve if chemotherapy and other treatments did not suppress the immune system.
The research team, led by Timothy P. Cripe, Nationwide Children’s Hospital, used a mouse model of rhabdomyosarcoma (a type of sarcoma), and found that T cells can be as crucial as viral therapy injections against tumor cells.
The results showed that virotherapy does not always require a heavy viral infection of cancer cells to make tumors shrink or die. Instead, the synergistic effect of the immune system may benefit viral therapy.
“Most work done in this field has tested virotherapy in human tumors implanted into mice with defective immune systems. If the only effect of the virus is to infect and kill the tumor cells, that should be fine. But if the immune system’s T cells play a role, we wouldn’t see their impact, since these mice don’t have T cells,” explained Dr. Cripe in a news release.
Researchers were concerned with the fact that viral therapies have a smaller impact in mouse cells than human cells; this could mean their research would not truly reflect the complexity of the disease in humans. However, there are some instances when human tumors are also difficult to infect. As such, understanding the way cells respond could reveal crucial information to further advance cancer treatments.
In collaboration with researchers from the Cincinnati Children’s Hospital Medical Center, the University of Pittsburgh School of Medicine and The Ohio State University, Dr. Cripe and his team tested oncolytic viral therapy against tumor cells in mice with a healthy immune system but also in immunocompromised mice.
“Despite the low infection levels of mouse cells with oHSV, we were able to cause a delay in tumor growth in one of the cancer models and even cure many of the mice in a second model. Even a small amount of infection with oHSV appears to be enough to trigger an immune response to the tumor,” study’s first author, Dr. Jennifer Leddon, added in the news release.
In immunocompromised mice, viral therapy did not have a great impact, indicating that even limited viral infection of tumor cells could stimulate T cells to attack tumors on its own. Some patients could actually respond to therapy even if the tumors were not very infectable by the virus, due to the efficient activation of their immune systems.
“Our data suggest that immunosuppression may not be the best strategy to help virotherapy do its job. In the past, we assumed a healthy immune system would fight off the virus infection before it could cause tumor shrinkage. But a healthy immune system might actually be helpful to virotherapy,” said Dr. Cripe.
Further research is necessary to understand the clinical implications of this phenomenon. “The effective immune response didn’t happen in every tumor model we tested, so we still need to figure out exactly what triggered the tumor shrinkage and how to predict which tumors will shrink in response to virotherapy,” added Dr. Leddon.
