Cancer Killing Viruses: The What? The How? & The What if?

Treating cancer has been puzzling doctors since antiquity. With the first unsuccessful attempt at surgically removing a tumour being nearly 4,000 years ago in ancient Egypt, the field of cancer biology has certainly come a long way. In order to combat a disease like cancer, an entirely new paradigm-shifting approach to medicine, “Gene Therapy”, has shown remarkable success in curing certain types of cancers in adults as well as in children and has saved millions of lives across the world. 

The most notable advancement in the field of cancer immunotherapies is without a doubt: the advent of CAR-T cells or 'Chimeric Antigen Receptor T-cells'. CARs are engineered receptors that effectively redirect T cells to cancer surface proteins that express a particular target biomarker. The unprecedented success of the anti-CD19 CAR T-cell in curing leukemia and lymphoma resulted in the approval of the first CAR-T cell therapy by the US-FDA in 2017. While CAR-T cell therapy demonstrates remarkable efficacy, it is accompanied by notable caveats, including cytokine release syndrome (CRS), a severe systemic inflammatory response; immune effector cell-associated neurotoxicity syndrome (ICANS), which can impair neurological function; and B-cell aplasia,  resulting in prolonged immunodeficiency due to the loss of healthy B-cells (specific to the popular anti CD-19 CAR-T cell therapy). 

Viruses have been seen as harbingers of mass destruction throughout history. Not long ago, we witnessed the biggest threat to our existence with the outbreak of Covid19. With more than 7 million lives lost, hundreds of millions suffered the impact of the pandemic. While this narrative paints viruses in a negative light, cancer researchers are using them as novel weapons in targeting cancer cells & eradicating them. Imagine Thanos, from the Blockbuster movie 'Avengers: Infinity War' a being who quite like a pandemic, wiped out half the people on Earth, reprogrammed to fight off any future invader.

Engineering viruses to combat cancer, i.e. oncolytic virotherapy, is a new and upcoming field that has the potential to transform cancer care. Viruses, majorly herpes simplex virus and vaccinia virus, are engineered to replicate in tumour cells. This leads to cancer cell death, leaving the body's cells unharmed. Upon tumour cell lysis, the virus can release tumour-associated antigens, which stimulate the immune system and induce immunogenic cell death, triggering anti-tumour immune responses. 

Oncolytic viruses are perfect for controlling tumour growth and show promise for possible integration of oncolytic viruses with CAR-T or CAR-NK therapies. According to numerous studies, a combination approach using oncolytic virus and cell therapies such as CAR-T or CAR-NK has the potential for long-term cure of multiple types of cancers through increased cytokine and chemokine levels within tumours, recruited CD8⁺ T cells to the tumour microenvironment, and transformed immunosuppressive tumours into immunosensitive ones. 

In conclusion, the synergy of oncolytic virotherapy and CAR-T cell technology heralds a new era in cancer treatment. By harnessing the destructive power of viruses and re-directing our immune system to recognize cancer, there is a potential to defeat cancer by this remarkable combination strategy. This synergy, while still in its infancy, paves the way for groundbreaking advances that could redefine oncology in the years to come.