Adapting to the changing landscape of cancer.
E. Antonio Chiocca, MD, PhD
Brigham and Women’s Hospital
“Cancer is not a defined or fixed entity,” says E. Antonio Chiocca, MD, PhD, neurosurgeon-in-chief and chair of the Department of Neurosurgery at Brigham and Women’s Hospital (Boston, MA). “Cancer evolves, grows and changes over time, which means effective treatments need to be able to respond in kind. They cannot be stationary or limited in scope. They must be able to adapt to the changing landscape of cancer.”
It is at this moving target that Dr. Chiocca has been taking aim since 1991. In the crosshairs are glioma stem cells, which Dr. Chiocca compares to a queen bee in a beehive in that “they are the source that gives rise to all other cancer cells in a tumor.”
Dr. Chiocca’s strategy combines three important elements, beginning with harnessing the power of viruses. “Viruses are interesting creatures. Most people think of viruses as things that cause disease, which they are, and which is why they can be valuable to us – we can direct them to cause disease in tumors. We engineer them to attack cancer cells and spare normal, healthy cells, and because viruses are flexible and adaptable, they can attack multiple mutations of cancer cells.”
In the process, viruses also engage a patient’s immune system to join the fight against cancer. This second component of Dr. Chiocca’s plan has a lasting ‘vaccination effect’ that enables a patient’s immune system to continue to recognize and fight cancer cells long after the original virus cells have diminished.
With funding from Alliance for Cancer Gene Therapy, Dr. Chiocca successfully conducted preclinical toxicity studies to determine the safety of this innovative approach. The research enabled him to complete the initial science and generate the data necessary to apply to the U.S. Food and Drug Administration for permission to put his strategy to the test in a phase one clinical trial.
In the wake of his successful Alliance-funded studies, Dr. Chiocca published several comprehensive reviews of the field in high profile journals, including Neuro-Oncology, Nature Medicine, Nature Reviews Clinical Oncology and JAMA Oncology.
Dr. Chiocca is still building on the foundation of knowledge validated by his Alliance-funded research. His first clinical trial is nearly complete and results appear promising. He is now poised to amplify his strategy with the third element of his plan – the integration of chemotherapy prodrug cyclophosphamide (CPA).
CPA is a well-known chemotherapy drug that Dr. Chiocca believes will improve the effectiveness of the virus on the tumor and assist in stimulating a patient’s immune response. Dr. Chiocca is preparing to put this third line of defense to the test soon in a phase two clinical trial.
Update: Following Dr. Chiocca’s first ACGT grant, he received a second one to develop and test a “next-generation” oncolytic virus for patients with glioblastoma. The funding from ACGT will help Dr. Chiocca perform studies requested by the FDA to show that this new oncolytic HSV possesses a safety profile that allows dosing in human patients. These studies will allow Dr. Chiocca to file an Investigational New Drug application to the FDA that will permit him to start a new clinical trial.
“Cancer is not a defined or fixed entity. Cancer evolves, grows and changes over time, which means effective treatments need to be able to respond in kind. They cannot be stationary or limited in scope. They must be able to adapt to the changing landscape of cancer.”