(From the August 2015 issue of Research Now)
The current survival rate for children under 3 years of age with atypical teratoid/rhabdoid tumors (AT/RTs) is 15 percent. Now, virotherapy may offer new hope for improving outcomes for patients with these highly aggressive tumors. A recent study published in Neuro-Oncology shows that a modified measles virus is an effective therapeutic agent against in vitro and in vivo models of atypical teratoid/rhabdoid tumors (AT/RTs).
“Measles virotherapy represents a novel therapeutic approach to treat AT/RT, where traditional therapies have failed, primarily due to the young age at diagnosis and the aggressive nature of the tumor,” says Adam Studebaker, PhD, a research scientist in the Center for Childhood Cancer and Blood Diseases at The Research Institute at Nationwide Children's Hospital and lead author on the paper.
According to Dr. Studebaker, AT/RTs are highly malignant, aggressive tumors that do not respond well to chemotherapy and primarily affect children under 3 years of age. Radiation does appear to have some effect, he adds, but patients this young traditionally do not get radiation to their central nervous system due to significant neurocognitive and endocrine defects.
The study showed that intratumoral administration of the modified measles virus (MV) significantly prolonged the survival of affected animals of primary and disseminated AT/RT disease. In fact, four of nine mice with localized disease survived to the experimental endpoint of 100 days and had no sign of viable tumor cells at autopsy.
When using intravenous (IV) delivery methods, research has demonstrated that results vary depending on treatment timing and frequency. Specifically, a one-time IV delivery of MV in both primary and localized models failed to significantly increase survival of animals, while IV treatments every other day for a total of three treatments did increase survival in primary disease models.
“Examining how virotherapy treatments work when administered through an IV is critical to clinical application,” says Timothy Cripe, MD, PhD, chief of the Division of Hematology, Oncology and Blood and Marrow Transplantation at Nationwide Children’s.
An IV delivery method is clinically appealing because of the ease of treating with an IV versus an injection into a brain tumor.
Although research regarding MV with AT/RT is still in animal models, virotherapy in general is gaining steam.
“There are already reports of treatment response following virotherapy: measles virus in multiple myeloma, herpes simplex virus in melanoma and poliovirus in glioblastoma multiforme,” says Dr. Studebaker. “As more clinical trials are initiated, I believe we will see additional treatment responses.”
“There is still a lot to learn regarding the interplay between oncolytic virotherapy and the host immune system,” Dr. Studebaker explains. “Most investigators believe you need both components: virus killing of cancer cells and then tumor immunity. Tumor immunity would kill remaining tumor cells as well as provide memory against relapsed tumor.”
Dr. Cripe agrees. His research studies focus on using herpes simplex virus to combat solid tumors in pediatric patients, including a phase I clinical trial on the safety of HSV for non-brain solid tumors.
“Using viruses to combat cancer is part of a new era in cancer therapy,” says Dr. Cripe, who is also a principal investigator in the Center for Childhood Cancer and Blood Diseases in The Research Institute at Nationwide Children’s. “While virotherapy is not new, modern genetic technologies are enabling resurgence in the field.”
In an editorial on the future of virotherapy, Dr. Cripe discusses how FDA approval of live-virus therapies could change the future for pediatric cancer patients. While virotherapy might be curative in some cases, it is more likely that it will be used as an adjunct with traditional therapies including surgical resection, chemotherapy and radiation.
“We are still determining which viruses are best at fighting which cancers and what techniques are best to deliver the viruses,” Dr. Cripe says. “We still have a lot to learn about using viruses against pediatric cancers.”
Studebaker AW, Hutzen B, Pierson CR, Shaffer TA, Raffel C, Jackson EM.Oncolytic measles virus efficacy in murine xenograft models of atypical rhabdoid tumors. Neuro-Oncology. 2015 Apr 2. [Epub ahead of print]