Alessandra Tomasi received her B.A. from Cornell University and is now a first-year medical student.
We have previously discussed the potential treatment of glioblastomas using targeted immunotherapy against cytomegalovirus. A 2014 study also conducted at the Duke University Medical Center in Durham, North Carolina has pioneered investigations of the efficacy of another new approach to tumor treatment, also centered around a virus. This time, the treatment seeks to use a recombinant form of human poliovirus, the causative agent of polio. PVS-RIPO is the name of a genetically recombinant, live attenuated (non-pathogenic), oncolytic (tumor-killing) virus that only spreads in susceptible, non-neuronal cells, thereby rendering it highly specific to glioblastoma (GBM) tumors.
In order to be effective, oncolytic viruses in general must accomplish the following once they reach a tumor: (1) they must destroy a “cancer shield” that keeps the immune system from attacking the cancer cells, and (2) they must physically attack and kill the tumor itself. To do so, Duke’s modified poliovirus was first genetically modified virus to contain a portion of the rhinovirus genome. Rhinoviruses cause the common cold, which is obviously a much less severe infection than polio. This modification prevents the poliovirus vector from replicating, reverting, or actually causing polio. The virus is then infused directly into a patient's brain via placement of a catheter, in order to maximize the amount of virus that will reach a tumor for efficacious targeting and killing.
The modified poliovirus has tumor-specific binding (i.e. it will reach and attack a tumor) because cancer cells express receptors that directly attract the poliovirus. Viral infections always require some sort of receptor to which the virus can bind and initiate infection. CD155 is a transmembrane protein found on the surface of certain non-neuronal cells in humans. CD115 is more commonly known simply as the poliovirus receptor given its involvement in viral adherence and infection, but, conveniently, it also plays a role in mediating tumor cell invasion and migration. Once the modified PVS-RIPO reaches its target cells, it attaches to CD155 to establish “infection,” then enters the cells (for any biologists out there, it exploits a ribosomal entry site for internalization). In this way, the modified virus harnesses a patient’s own immune system to fight cancer by eliciting an inflammatory response. This response includes the recruitment of various immune cells to initiate a cascade that will eventually – hopefully – lead to tumor cell death.
Our bodies have the means to destroy certain kinds of cancer cells via the immune system’s many powerful components that can work synergistically to defeat an unwanted visitor. It’s quite possible that the future of cancer treatment is a matter of triggering a targeted, amplified immune response at the site of a budding tumor.