Oncolytic viruses have never been shown to work systemically to induce a complete remission of metastatic cancer - until now. A group at the Mayo Clinic in Rochester, Minnesota has used a modified measles virus to send one patient into complete remission who has now been disease-free for over six months giving hope that viral therapies can be effective against cancer.
Injecting someone with a virus to cure cancer sounds kind of counterintuitive, right?
Well, that just what researchers at the Mayo Clinic in Rochester, Minnesota have reported to do in a brief report.
They didn’t just use any virus though. They used a modification of the attenuated virus that’s used across the world in measles vaccines. By attenuated, I mean the virus, while isolated from a patient, David Edmonston, in 1954, has since been passaged in tissue culture and selected for reduced pathogenicity. Remaining “alive,” this virus can replicate to an extent in humans allowing them to build up a memory immune response against the virus in case a wild type virus ever comes our way without inducing a full-blown infection.
By further growing this virus in HeLa cells, human cancer cells originally isolated from an African American woman, Henrietta Lacks, in 1951, they selected for the virus to be able to grow in human cancer cells thus promoting its targeting to cancer cells. They additionally designed the virus to express a sodium iodide symporter that can transport iodide into the cell to allow for imaging the localization of the virus-infected cells using radioactive iodine.
While the idea of using oncolytic viruses that can infect and kill cancer cells is not a new concept (research efforts began in the 1960s with the idea arising much earlier), their study serves as a proof of principle that these viruses can be used systemically against the deadly cancer multiple myeloma rather than by injection into a localized tumor.
Currently in phase I trial, this virus, known as MV-NIS (measles virus sodium-iodide symporter), showed remarkable results in two patients. While only one had a complete remission, the other still had localization of virus to the tumor and a partial response.
So how does this work exactly? The idea behind oncolytic viruses is that they will selectively infect cancer cells, and following their replication within the host cell they will cause it to rupture so that they can go forth and infect other cells. By lysing cells in this manner, these viruses can decrease tumor mass as shown in this study.
An additional mechanism for destroying the tumor comes from the immune recognition of these viruses. As a non-self entity, the virus can elicit a specific immune response to destroy the virus and any cells infected with it that would present virus-derived antigens.
While this immune response provides an additional mechanism to clearing the tumor, it also creates a limitation to the therapy. The attenuated virus is able to repeatedly replicate within tumor cells, lyse them, and go on to infect other cancer cells. With an immune response though, the infected cells are destroyed along with the virus meaning it can no longer continue to infect cancer cells. Therefore, the immune system recognizes and destroys only those cancer cells with actively replicating virus.
In the case of this measles vaccine-based therapy, it was essential to select patients that were seronegative for prior measles exposure to best avoid this limitation, which restricts the patient pool that is able to receive this therapy. This is a major challenge that will have to be faced in the design of future oncolytic virus therapies.
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Image: "Figure 1" from Zulkifli Mustafa, Hidayah Roslan and Jafri Malin Abdullah (2011). Targeted Therapy for Gliomas: the Oncolytic Virus Applications, Brain Tumors - Current and Emerging Therapeutic Strategies, Dr. Ana Lucia Abujamra (Ed.), ISBN: 978-953-307-588-4, InTech, DOI: 10.5772/23777. [OPEN ACCESS]
