Viruses for cancer therapy
Oncolytic adenoviruses are known to preferentially infect and destroy cancer cells while leaving normal cells unharmed. Despite what was initially envisaged, oncolytic viruses do not merely lyse tumour cells but they also induce host immune responses against cancer cells. Scientists on the EU-funded IMMUNOTHERAPY project decided to exploit this feature for generating long-lasting anti-tumour immunity. To this end, they engineered adenoviruses to express the cytokine called granulocyte-macrophage colony-stimulating factor and attract antigen presenting cells at the tumour site. This approach essentially turns lysed tumour cells into a vaccine and induces systemic immunity against the tumour. Administration of the virus in various preclinical models generated very promising results with respect to anti-cancer efficacy and also provided a long-term vaccine effect. Based on this data, researchers proceeded with testing this virus in a clinical trial in cancer patients who were refractory to standard therapy. Modifications of the virus and co-administration with chemotherapy further improved the therapeutic outcome. This combinatorial approach was found to reduce the number of regulatory T cells that were present at the tumour site. As an alternative strategy for enhancing immune responses, researchers explored the toll-like receptors (TLRs) that are known for their role in innate immunity. They successfully engineered a novel oncolytic adenovirus to stimulate TLR9 on dendritic cells and bring about T cell activation. Engineering a 'super' virus is being considered as a long term plan for treating cancer. By combining TLR-mediated activation and immunomodulatory molecules, the IMMUNOTHERAPY strategy boasts enhanced tumour clearance.
