New Way to Reprogram Macrophages Helps Immune System Kill Tumors

Macrophages, as their greek-derived name implies, are hungry white blood cells that consume all kinds of foreign and unwanted objects within the body. They are one of the primary methods that the immune system uses to fight off disease, and they work by checking the protein content on the exterior of cells to identify whether the cells are native or are invaders. In terms of cancer, macrophages, unlike T-cells, are able to penetrate solid tissue but are often a long way from being effective, ignoring diseased cells because the proteins on their outer layer match the ones found on healthy cells.

At the University of Pennsylvania researchers have now come up with a strategy to modify macrophages so that they are able to spot cancerous cells. This may open a new front against solid tumors, as previously developed immunotherapy methods to fight cancer have been mostly effective against so-called “liquid” tumors that are hematologic in origin.

The team modified the nature of macrophages to remove a mechanism that cancer cells use to pretend that they’re healthy. Specifically, they removed a protein on the surface of macrophages called SIRPA that interacts with a protein called CD47 that native cells use to tell the macrophages they’re on the same team. Since tumor cells exhibit the same CD47 protein in many cases, macrophages are fooled into ignoring them.

In addition to the macrophages, the team also introduced antibodies via an injection that seek out tumor cells and help to alert the immune system. The combination of a warning mechanism by the antibodies and an ability to distinguish the cancerous cells by the macrophages made the combination very powerful in killing cancer.

The team tested their approach in laboratory mice that exhibited human cancers and demonstrated that the modified macrophages were able to penetrate tumors and reduce their size by up to 80 percent. At the same time they did not notice any increase in toxicity, hopefully pointing to the safety of the technique, something that will still have to be verified in further studies.

Study in journal Current Biology: SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors…

Via: UPenn…