Carnegie Mellon University, approaches immunotherapy differently.Immunotherapy brings to mind monoclonal antibodies, immune system modulators, and cell-based therapies, but Dr. Elizabeth Wayne, an assistant professor of Biomedical Engineering and Chemical Engineering at
Wayne investigates how to turn immune cells into drug-delivery vessels capable of targeting any location in the body. She focuses on macrophages, an understated but key cell type in the immune system repertoire. Using the principles of engineering and nanotechnology, she transforms the immune system into a drug delivery system capable of restoring balance, providing readouts, and reshaping the tumor landscape.
DDN Magazine: How did you become interested in immuno-engineering?
Elizabeth Wayne: Ninety percent of cancer deaths are attributed to metastasis. I wanted to know what happens when tumor cells leave the primary tumor and go to a second site, like the brain. So I hatched this big scheme to image cancer cells as they invaded the brain and the immune cell responses to that process.
The brain is big compared to a cancer cell, and I did not see a lot of metastatic cells. But what I saw after five years of working in a basement with a microscope and looking at mouse brains was that immune cells are incredibly active. They respond to hypoxia changes. They migrate, proliferate, and perform many processes. I started switching my gears from thinking about things as an engineer, where cells are just spheres, to thinking of cells as receptors and sensors that migrate and collaborate with other cells. I realized that it could be useful to pair engineering principles with immunology. Many engineers are coming to terms with the fact that we cannot conquer the immune system; we have to work with it.
DDN: Why did you choose to study macrophages?
Wayne: Macrophages maintain homeostasis among the cell types of the immune system. Based on their environment, macrophages decide whether to become pro-inflammatory or anti-inflammatory, and when they are not functioning properly, there is chaos. You see this playing out in diseases such as neurodegeneration and cancer. We want to understand the biology of macrophages, their responses to the cues around them, and how to use nanoparticles and nanotechnology to switch macrophage phenotype and regulate the inflammation process.
DDN: Why are macrophages useful for studying cancer?
Wayne: Depending on tumor type and stage, macrophages make up 30 percent to 90 percent of a solid tumor. They migrate to tumors and really shape the immune environment. T cells do not really penetrate solid tumors, whereas macrophages do. We can target macrophages to change the immune environment to make it more permissive for T cell therapies.
There are two populations of macrophages; one is a tissue derived population. For example, there are breast macrophages, but monocytes from the blood, which may become macrophages, also migrate to tumors, offering two different target types.
Finally, in cancer, CD8 T cells and macrophages behave like regulatory T cells. We plan to reverse that phenotype to push them towards the TH1 pro-inflammatory phenotype, where M1 macrophages secrete cytokines, undergo phagocytosis, and promote CD8 killer T cell infiltration. Macrophages are important for T cell treatments. They are important to change the tumor microenvironment. I am also interested in using macrophages as a cellular theranostic.
DDN: What is a theranostic?
Wayne: Theranostics combine therapy and diagnostic technologies. Monocytes migrate to the tumor, so I would like to attach drugs to them, or assay the monocytes and use them as a readout of drug effectivity. I can observe how macrophages change their function and phenotype after drug administration. If the drug cued macrophages to become more active, then the therapy worked.
DDN: What is the most important challenge in your field?
Wayne: The biggest challenge goes beyond macrophage therapy. We need to determine who needs what therapy and when they need it.
Another big challenge is searching for a common antigen. For example, chimeric antigen receptor T cell (CAR-T) therapy has a lot of benefits, but we need to target it to something. Finding antigens in cancer is challenging, particularly in solid tumors.