Viruses, when engineered, may have the potential to alter the course of cancer by driving tumor cells to express novel viral antigens or enhance the production of existing tumor antigens.
The research and understanding of viruses have led to the discoveries of vaccines and opportunities to use the virus for therapeutic purposes. Viruses, when engineered, may have the potential to alter the course of cancer by driving tumor cells to express novel viral antigens or enhance the production of existing tumor antigens, according to a recent article published by The New England Journal of Medicine.
The authors, Dan L. Longo, MD, and Lindsey R. Baden, MD, discussed xenogenization, or making a tumor more foreign by boosting the recognition of tumor cells by the host immune system. The authors suggested that this effect can be used to create more effective cancer vaccines.
“As a result of intense study, we have learned how viruses cause disease, which genes are responsible, and how they work. The resultant discoveries have led to the development of improved vaccines and the development of strategies to exploit features of viruses for therapeutic purposes,” the authors explained. “For example, the ability of viruses to transfer genetic material to target cells has enabled physicians to correct inherited gene defects in clotting factors, globin genes, and metabolic enzymes and to arm T cells to search for and destroy tumor cells.”
The article explained that oncolytic viruses are capable of infecting lysing tumor cells, and these viruses can kill tumor cells directly, while the host response to the dead cells can lead to an effective immune response against any other tumor that was not killed by the virus.
“The resulting immune response includes both innate (antigen-nonspecific) and adaptive (antigen-specific) components,” noted the authors. “Among the intrinsic barriers to using these viruses therapeutically are the host defense system, uncertain distribution between normal and tumor tissues, and intrinsic resistance of cells to viral infection.”
A previous study demonstrated the use of an engineered poliovirus, called PVSRIPO, to target glioblastoma, the authors noted. Poliovirus is a single-stranded RNA-containing picornavirus that gains entry to cells through CD155, a receptor that is increased in expression on glioblastoma cells. Specifically, in the study PVSRIPO was modified by the replacement of the viral internal ribosome entry site which prevented viral replication in healthy neuronal cells.
Additionally, at Duke University, researchers treated 61 patients with glioblastoma using PVSRIPO, according to the article. At 2 years of follow-up, the survival curve reached a plateau that has been maintained with a survival rate at 36 months of 21%, while the control group had 4% survival rate at the time.
“An interesting feature of the study design was to vaccinate the patients with the polio vaccine before treatment,” the authors stated. “This ensured that systemic poliovirus serotype 1 immunity was present at the time of instillation of PVSRIPO into the glioma, reducing the risk of spread of the experimental virus beyond the tumor.”
The authors emphasized that there is more research needed on the efficacy of viruses to treat cancers; however, the previous clinical results have demonstrated the potential of this treatment approach.
Longo DL, Baden LR. Exploiting viruses to treat diseases. N Engl J Med. 2018; 379: 194-196. doi: 10.1056/NEJMe1807181.