POlyhedrin Delivery System (PODS) technology from Cell Guidance Systems has been shown to modulate macrophage secretion profiles with therapeutic potential. The results of this research are available as an unpublished preprint in bioRxiv.
Macrophages play a significant role in directing a body’s fight against disease with capacity to switch activity to also help rebuild damaged tissues. However, as diseases such as cancer develop, macrophage activity is subverted, and the secretion of cytokines that would normally activate anti-cancer activities of other immune cells is stopped. As a result, macrophages begin to contribute to the development and spread of cancer. To compensate for the reduction in cytokines and to correct the imbalance, targeted approaches are needed as simply injecting cytokines into the body generates high levels of systemic toxicity.
To address this, Cell Guidance Systems’ scientists say they ‘fed’ macrophages with nanoscale chunks of concentrated protein in the form of PODS crystals - solid cubes able to hold a variety of cytokine cargos which can be ingested by macrophages without adverse effects to the macrophage itself.
PODS are packed with protein and the macrophages cannot completely break them down. Instead, this research reveals, the macrophages secrete a constant stream of bioactive cytokines with the ability to instruct adjacent cells. This ability to restore and increase cytokine levels could have therapeutic potential to treat diseases which lead to reduced macrophage cytokine levels, such as cancer.
The company theorises many potential applications of PODS-loaded macrophages. Currently, they are used to study complex cellular interactions and other phagocytic cells, such as chondrocytes. Ultimately, Cell Guidance Systems claims PODS-loaded macrophages have potential to improve cytokine treatments for diseases.
“Macrophages are well known for their ability to engulf pathogens. These remarkable cells are both the body’s soldiers and builders: apart from fighting disease, they have a unique capacity to change their activity to help rebuild damaged tissues,” said Dr Michael Jones, CEO of Cell Guidance Systems. “Although highly potent, cytokines can be very toxic. This has really limited their use to treat disease. With a few exceptions, cytokines need targeted delivery and what is unique about our approach using PODS with macrophages is the ability to deliver specific cytokines from macrophages to surrounding cells. It is very exciting as there is likely therapeutic potential, particularly in diseases such as cancer.”
