One of the newest and most exciting approaches to immuno-oncology is oncolytic virotherapy. In recent years, an increasing number of researchers have begun experimenting with oncolytic virotherapy and its immunotherapeutic applications. The connection between cancer suppression and viruses was first noted in the mid-20th century, but the connection wasn’t further analyzed until recently, under the banner of advanced genetic engineering techniques. Today, scientists have found that virotherapy can be used to attack and destroy cancer cells.
The modern approach to oncolytic virotherapy involves modifying viruses so that they have the ability to selectively target cancer cells with particular biomarkers, rather than the body’s healthy cells. These oncolytic viruses could be less susceptible to immune suppression techniques that allow tumors to evade normal immunological processes. Moreover, these viruses are programmable to the point where they would target specific classes of cancer. From an immunological perspective, oncolytic viruses can potentially be used to insert and express various cancer-suppressing genes and proteins that have diagnostic applications.
Oncolytic Viruses Show Promise in Preclinical and Clinical Trials
Researchers have had some exciting successes with oncolytic viruses in the last few years that speak to the potential of the therapy. Both preclinical and clinical trials have evaluated genetically engineered oncolytic viruses targeting different forms of cancer. One promising approach delivered a modified herpes simplex virus directly into melanoma and head and neck tumors. Researchers have also used reovirus in combination with chemotherapy to treat certain cancers. In addition, vaccinia viruses have been delivered intravenously and intra-tumorally to treat solid tumor cancers. A large number of preclinical studies are looking more closely at these viruses and others to identify potential combination approaches.
In general, oncologists are reaching an agreement that oncolytic virotherapy is a viable option for the future of cancer treatment. The body of medical and scientific evidence supporting this belief grows larger every day. With more research, the approach has real potential to improve quality of life for people with cancer, as well as ultimate outcomes.
What Exactly Are Oncolytic Viruses and What Do They Do?
An oncolytic virus is bioengineered to target specific cancer cells based on characteristic biomarkers. When the virus comes in contact with a tumor cell, it induces lysis and kills the cell. Because the viruses are specific, they leave non-cancerous cells unharmed, unlike traditional approaches to cancer treatment, such as radiotherapy and chemotherapy. While oncolytic viruses are naturally attracted to cancer cells, a number of questions remain about the safety of their use in certain patient groups, as well as their replication abilities and selectivity. These characteristics change according to the type and strain of virus used in the therapy.
Scientists need to conduct further research to understand how each virus functions in oncolytic virotherapy. Some of the most common viruses currently under study include the herpes simplex virus, vesicular stomatitis virus, adenovirus, vaccinia virus, reovirus, and Coxsackie virus.
Some oncolytic viruses may be capable of destroying cells that are resistant to traditional radiation and chemotherapy treatments, as shown by a few recent studies. Researchers have also suggested that synergistic effects exist when combining the viruses with these traditional approaches, and that some oncolytic viruses can carry therapeutic or diagnostic molecules directly into tumors in a way not previously possible. Furthermore, some research suggests that oncolytic viruses actually trigger an immune response against the tumor via a cytokine release that attracts natural killer cells.
In 2005, the first oncolytic adenovirus was approved for human use in China. This approval set the stage for research into more effective and safer therapies in recent years.
What Challenges Still Exist in Designing Oncolytic Viruses?
Before we see oncolytic viruses become a widespread cancer therapy in the United States, researchers must tackle several challenges. To be effective, a particular virotherapy must be highly selective, meaning that it preferentially seeks out and targets tumor cells while leaving non-cancerous cells alone. Successful oncolytic viruses must also be replication-competent; the virus must have the ability to make copies of itself, since such amplification is critical for destroying tumor cells. However, the virus should carry no risk of genomic integration. Some viruses can integrate into the host cell DNA, so only oncolytic viruses that replicate in the cytoplasm can be studied, in order to avoid the risk of mutation.
Of course, the virus should be well-tolerated within the human body. Cancer patients are often immuno-compromised, so side effects should ideally be minimal. Importantly, the virus cannot be pathogenic. The virus should work synergistically with the body’s immune system to maximize the virus’ spread and attack on the tumor.
Specific strains of oncolytic viruses are able to insert and express cancer-suppressing genes or carry anti-cancer therapies directly to the tumor. Scientists must study this ability further, so they can leverage it as a way to overcome cancer’s ability to sidestep normal immune responses. This ability becomes even more important when the virus can be administered systematically rather than locally. Then, the virus would seek out and attack all tumors and metastases.