Oncolytic viruses: Using bio-engineered viruses to fight cancer
By: Forrest Anthony, MD, PhD | June 02, 2017
How innovative oncology researchers are using deadly viruses to treat cancer.
In the battle against cancer, immunotherapies are the new warriors. These treatments harness the body’s own immune system to destroy cancerous cells, and for some patients with some types of deadly cancer, these new therapies are giving patients new hope for longer lives.
The American Society of Clinical Oncology (ASCO) named Immunotherapy the Advance of the Year in its Twelfth Annual Cancer Progress Report; and this year’s annual ASCO Annual Meeting in Chicago (June 2-6) will feature many presentations and posters exploring a number of immunotherapy innovations.
One particular kind of immunotherapy, using live viruses to kill cancer cells and stimulate systemic immunity, is receiving renewed attention, and these agents are called oncolytic viruses. Like cancer vaccines, oncolytic viruses are an old idea, but never really worked well enough to be practical, until we had a better understanding of the immune system. Now, new kinds of engineered “oncolytic” viruses have been scientifically proven in clinical trials to be safe and effective for some cancer patients. As the cancer cells are destroyed they release new infectious particles that attack remaining tumor cells, while also stimulating a generalized immune response to the tumor type. A variety of viruses have been developed as oncolytic agents, including measles, adenoviruses, herpes simplex, and Newcastle disease virus, which are engineered for safety and tumor selectivity.
Several of these treatments are currently in development, with the first gaining approval from the US Food and Drug Administration in 2015. These include Amgen’s Imlygic™ (talimogene laherparepvec or T-Vec), a genetically modified oncolytic viral therapy for patients with melanoma recurrent after initial surgery. T-Vec, which is a genetically modified herpes simplex virus type 1, is the first oncolytic viral therapy approved by the FDA based on therapeutic benefit demonstrated in a pivotal study.
Many of these therapies are being tested in combination with checkpoint inhibitors, to create synergies between treatments to more effectively fight a broader variety of tumor types. For example, at the ASCO meeting, experts from the Huntsman Cancer Institute at the University of Utah, will present the results of a study of a combination therapy using an oncolytic virus and ipilimumab in patients with stage IIIB-IV unresectable or metastatic melanoma.
In some cases these combination therapies use multiple mechanisms of action to attack certain tumor types, such as pancreatic ductal adenocarcinoma (PDAC), which are non-responsive to individual treatments; while in other cases they provide a more powerful cancer fighting response than from single treatments alone, such as the combination of paclitaxel for breast cancer treatment.
Oncolytic viruses clearly offer benefits for some cancer patients with some tumor types, however this approach also faces considerable obstacles. Working with pathogenic viruses is always risky, particularly when patients are already immune-compromised. These treatment are also expensive and challenging to safely manufacture and distribute, especially on a global scale.
The interesting irony here is that viruses, which can cause deadly human infection, can actually be “engineered” to become allies in treating a different type of deadly human disease, cancer. After many years of research, the first such oncolytic virus product is now approved, and others are being developed. For example, last year, scientists at Duke University Medical Center developed a genetically engineered form of poliovirus to attack deadly glioblastoma brain tumors. It showed such promising phase 1 trial results that the FDA granted it breakthrough therapy designation as a potential treatment for patients with recurrent forms of the tumor, which are almost always fatal.
This is just one example of how oncolytic viruses, along with all of the other innovative immunology research, has the potential to improve lives of cancer patients. With continued investment in such promising immunotherapies, and diagnostic tools to determine which patients are most likely to respond, we can improve the outlook for cancer patients around the world.