USing viruses against childhood cancers
For over 100 years, scientists have been investigating reports of cancers
that have miraculously shrunk or disappeared after patients contracted certain
viruses. Can viruses cure cancer? If so, how?
Rapid advances in understanding cell biology have helped scientists not only understand the mechanism of viruses, but to genetically modify these viruses to be safe, stimulate a patient’s immune system and target and kill cancer cells. These are called oncolytic viruses.
Recently, the potential of oncolytic viruses to treat deadly cancers was featured in a segment of 60 Minutes, which highlighted the work of Matthias Gromeier, MD, at Duke University. Dr. Gromeier is using a modified version of the polio virus in adults with a deadly brain tumor known as gliomas. For more than 15 years, Dr. Gromeier has been carefully investigating and testing the affects of this novel oncolytic virus to teach the body’s immune system to recognize specific targets on brain tumor cells. The Duke clinical trial has enrolled 22 patients and shown promise in targeting and killing the deadly brain tumor cells. [watch the video here]
Solving Kids’ Cancer has been in discussion with Dr. Gromeier since 2012 to find a way to best bring this novel treatment option to children with deadly brain tumors. Additionally, since 2009, Solving Kids’ Cancer has initiated and funded two clinical trials and a research project to investigate the potential of oncoloytic viruses in children with the deadliest childhood cancers.
-JX-594, a virus strain derived from the same vaccine used to eradicate small pox, had previously been tested in for adults with cancer and shown benefit, which led Solving Kids’ Cancer to approach the researchers about creating a trial for children with solid tumors. In 2009, Solving Kids’ Cancer launched a clinical trial using the JX-594 virus in children with relapsed or resistant solid tumors, including neuroblastoma, Ewing’s sarcoma and liver cancer. The clinical trial was open at Cincinnati Children’s Hospital, Texas Children’s Hospital and Nationwide Children’s Hospital and results were recently published (1). Researchers believe that oncolytic viruses like JX-594 will be an important component in combination with other immunotherapies to put patients into durable remission.
- HSV1716 (Seprehvir) is a "first in class" engineered oncolytic virus derived from the herpes simplex virus, and is designed to target and destroy cancer cells. More than 70 adult cancer patients (brain cancer, head/neck carcinoma, melanoma) in Europe have received HSV1716, where it proved beneficial in early phase trials. Solving Kids’ Cancer brought this novel research to the U.S. and developed the first clinical trial, which opened for children in 2010. The trial is currently enrolling patients at Nationwide Children’s Hospital and Cincinnati Children’s Hospital.
-Solving Kids’ Cancer developed a novel program to screen a variety of wild-type rhabdoviruses and found that a modified virus known as Maraba MG1 was the most effective in killing neuroblastoma cancer cells in the lab. Maraba MG1 was tested in 11 neuroblastoma cell lines grown from patients, including isolated neuroblastoma cancer stem cells (tumor-initiating cells) identified by a previous Solving Kids’ Cancer-funded research project. This oncolytic virus is a potentially promising new therapy that merits testing in children with neuroblastoma.
Without a doubt, it is an exciting time in medicine as scientists make new discoveries in cancer research. The key will be to bring these novel therapies -- combination drugs, targeted therapies, precision medicine, immunotherapy or oncolytic viruses -- to more children with the deadliest childhood cancers through clinical trials.
For more information on the use of oncolytic viruses in childhood cancers, see a short review on INBRACED “International Neuroblastoma Research and Collaboration for Effective Delivery” Click Here to read
Mol Ther. 2015 Mar;23(3):602-8. doi: 10.1038/mt.2014.243. Epub 2014 Dec 22.
Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients.
Cripe TP1, Ngo MC2, Geller JI3, Louis CU2, Currier MA1, Racadio JM3, Towbin AJ3, Rooney CM2, Pelusio A4, Moon A4, Hwang TH4, Burke JM4, Bell JC5, Kirn DH4, Breitbach CJ4.