Viruses are now being used as anti-cancer agents. We will design a cancer therapy based on a virus called parainfluenza virus 5, which naturally infects the respiratory tract but is not associated with human disease. Using a mouse model system, we will combine a mutant version of parainfluenza virus which is specific for lung tumor cells and a type of normal human immune cell called Natural Killer (NK) cells, which recognize cancer cells and kill them. Through this combined approach we will harness the immune system's ability to recognize this novel virus to aid in clearance of lung cancer cells.
This project is based on our recent progress in development of a novel approach to use oncolytic viruses (which preferentially infect and kill cancer cells) to harness the power of NK cells for lung cancer therapy. In the past funding period, we identified the most effective viral vector for “marking” lung cancer cells for killing by NK cells. Using a novel real-time assay and 3-dimensional cultures of lung cancer cells, we have uncovered a two-step mechanism by which NK cells first kill the outer layer of virus-infected cells, but then proceed to continue killing un-infected lung cancer cells deep within the 3-dimensional culture. We plan to couple the viral-mediated deliver of “markers” with our 2-step model for activation NK cell-killing of lung cancer cells.