Grant: Project Grant

New cancer therapies are increasingly relying on cell engineering to achieve successful outcomes. For example, immune cells from patients are cultured, engineered and re-injected back into the same patient to re activate the immune system in some modern cancer therapies. These approaches work well in leukemia and other liquid cancers but not very well in solid cancers like pancreatic cancer and breast cancer. The question is why and how can we better understand what barriers the engineered cells are facing. The development of imaging tools that allow researchers to follow engineered cells at high resolution deep in tissue would provide a powerful means to fill in the knowledge gaps and test new hypotheses to improve therapy. One such tool is green fluorescent protein (GFP) which is a Nobel prize winning optical method to report on cell location and activity but this method only works at high resolution very close (millimeters) to the surface. Light scatter severely blurs information arising deep in tissue. The work in this proposal we will teach highly metastatic tumor cells to make their own contrast nanoparticles such that microultrasound imaging can detect their location and activity deep in tissue. The new nanoparticles are manufactured by acoustic reporter genes (ARGs) embedded in the genomes of specifically engineered metastatic cell lines. This novel research will be first applied to animal models of metastasis to learn how tumor cells spread to distant tissues such as the liver, lung, and other tissues. Comparisons with the optical approaches will be used to prove the benefits of acoustic reporter genes.