THE "GOOD" VIRUS By
ANNA ARGULIAN SWATHI BALAJI
With the onset of the 2020 COVID-19 pandemic, viral research has reached a historical peak. With every university dedicated to unraveling the mechanism behind coronavirus, and every ear attuned to the latest news, the world finally awakened to a long-forgotten and slumbering pathogen: the virus. Although many had forgotten about the versatility of viruses before the pandemic, behind the scenes research rapidly accelerated as modern technology began to cast viruses as vehicles of cancer remedy. Thus, the 21st century saw the rise of the very first “good” virus. Since the early nineteenth century and the advent of cancer treatment, case studies have uncovered the surprising effects of infection in cancer patients. Early reports have shown how coinciding viral infections had the potential to elicit temporary tumor regression and brief remission. A modern example can be seen in a recent Clinical Cancer Research publication, where a strain of the common cold was able to induce
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regression in bladder cancer. With this peculiar correlation, research into virology took a sharp turn in the 1950s but simmered down around the 70s and 80s due to the limiting nature of the approach. At the time, researchers knew too little about the mechanism of tumor shrinkage as well as the possible ways to correctly harness virology to combat cancer. However, with the recent advent of gene editing and further studies into the molecular pathways involved in carcinogenesis, a new revolution in viral immunotherapy began. A cancer prognosis is typically dependent on the present tumor microenvironment (TME). The TME can be classified into a “cold” and “hot” phenotype, where “cold” tumors are immune deserts, with minimal immune cell infiltration, and “hot” tumors are recognized by the immune system. Subsequently, the largest challenge of current immono-oncology is either turning a “cold” tumor into an immunologically responsive tumor or activating already present tumor immune cells that
have been previously inhibited by various cancer mechanisms. Thus, the attractiveness of viruses as clinical targets lies in their ability to elicit strong immune responses and bring in cytotoxic T cells to kill the infected tumor cells. Current research has targeted viral entry pathways specific to tumor cells in an effort to localize the therapy and ensure a minimized systemic effect. Furthermore, a majority of oncolytic viruses are genetically engineered to have deletions in their genome to reduce pathogenicity and instead insert various sequences that either increase specificity to the tumor or even function to produce chemotherapeutic toxins within the tumor. The year 2015 saw the very first FDA approved oncolytic virus, Talimogene Laherperepvec (T-VEC), developed by Amgen with the help of physician Igor Puzanov. Injected intratumorally, T-VEV is a modified form of the herpes virus, with two genes specifically removed that function to strengthen the virus against host immunity. The modified and
