By Christine Liu
Oncolytic virotherapy; the treatment of tumors cells with viruses
Oncolytic virotherapy uses viruses to target cancer cells, preferentially killing malignant tissue. Although the viruses we often hear about are known for their detrimental affects on cells, their ability to cause cellular dysfunction helps when the target is cancer. The viral genome readily accommodates the genetic modifications necessary to selectively target tumor cells, improve lytic abilities, and induce antitumor immunity in the host, while providing a safer alternative to current methods of chemotherapy. The potential efficiency and long term affects of viral therapies make this field attractive to scientists seeking better cancer treatments.
Scientists have modified existing viruses to target cancers with promising preclinical results. However, challenges remain in the execution of viral therapies, particularly when it comes to averting the innate immune system’s defenses. The body’s immune system can neutralize viral therapies, decreasing their effectiveness. Additionally, there are many safety concerns when it comes to using viruses, as they have the potential to cause infection to healthy cells or even other individuals. Even manufacturing these viruses needs more technological innovations in order to realistically produce enough.
The Seneca Valley Virus (SVV-001) has a selectivity for small-cell cancer cells and few existing antibodies in humans. This property makes SVV-001 a candidate for virotherapy, and has been studied in a phase I clinical trial to treat small cell lung cancer. Preliminary results of the trial showed the effectiveness of SVV-001 in both targeting only tumor cells and replicating itself. These findings are promising, as antitumor activity may lead to a long term solution. The virus was shown to be safe, with few side effects and no dose limiting toxicity.
I interviewed Dr. John T. Poirer, one of the main scientists of the clinical trial. Poirer, now an assistant professor, currently studies SVV-001 at the Memorial Sloan-Kettering Cancer Research Center. He has been working with SVV-001 since he was a graduate student.
In general, Poirer is optimistic with regard to the phase I trial results. The trial will help in proving the safety of viral therapies, and pave the way for the approval of other oncolytic virotherapy trials. Phase II trials are currently underway.
Dr. Poirer’s lab is currently trying to identify the cellular receptor to the virus, and pairing the virus with a protease-activated toxin. Although the identity of the receptor has been elusive, much progress has been made in designing a toxin to pair with the virus. Linde Miles, a graduate student working in Poirer’s lab, has been working on a toxin that will only be activated by virus infected tumor cells. This will increase the toxicity of the viral therapy.
The SVV-001 genome codes for one relatively long amino acid sequence, which is then cut into several functional proteins by a virus-specific protease. Miles has been working with short viral peptides and the viral protease to try and develop a toxin that will activate upon SVV-001 protease activity. Such a toxin would only affect infected cells, and because SVV-001 selects for small tumor cells, cancer cells will be killed while leaving healthy tissues unharmed. Miles has already identified the peptide sequence that the viral protease will cut, and is collaborating with chemists to develop the toxin.
The field of oncolytic virology holds great promise for treating cancer. Virotherapy can be long term, and has far less undesirable side affects than current mainstream cancer therapies. More research is necessary to fully realize this treatment, which will take time, and the success of viral therapies depends greatly on safety for both the patient and other individuals. While there is potential for viruses to target many tumor cells, it is more likely that only some cancers will have viral treatments available, until scientists discover better methods for designing other oncolytic viruses.
Rudin, C. M., Poirier, J. T., Senzer, N. N., Stephenson, J., Loesch, D., Burrounds, K. D., Reddy, P. S., Hann, C. L., & Hallenbeck, P. L. (2011). Phase I Clinical Study of Seneca Valley Virus (SVV-001), a Replication-Competent Picornavirus, in Advanced Solid Tumors with Neuroendocrine Features. Clinical Cancer Research, 17, 888.