Using Modified Macrophages for Targeting Cancer

One of the most exciting new areas for cancer treatment occurs at the intersection between the disease and the immune system. While the immune system has an inherent ability to detect and destroy abnormal cells, many cancers are able to produce signals and/or alter themselves to avoid this detection and destruction. Macrophages not only engulf and break down pathogens, they also stimulate immune cells, including other macrophages. The immune-stimulating functions of macrophages are silenced in cancer, and macrophages are recruited to disease sites, where they contribute to its development and progression. By targeting macrophages, we aim to both harness their immune-stimulating, cancer cell killing properties, and curtail their oncogenic activities.While macrophages have great potential as new targets for treating cancer, much about their roles and unique properties remain unknown. Macrophages have the ability to interconvert between immune stimulating and suppressing subtypes, but when and how these conversions occur cannot be elucidated using currently available techniques. We are engineering macrophages to possess reporters to discern phenotypes, which can be used in relevant disease models. We will also use this platform to find ways to convert pro-tumor macrophages into cancer fighting ones that will attack the tumor itself. Also because tumors generate chemical signals that serve to recruit macrophages, we are taking advantage of this characteristic and developing cell-based imaging and drug delivery agents via chemical modification of macrophage surfaces.