A common protein that kills cancer cells in the bloodstream works shows improved efficiency when bound to the surface of white blood cells, scientists report in the Proceedings of the National Academy of Sciences. Cancer cells that migrate from one place in the body to another through the bloodstream, in a process known as metastasis, are difficult to detect and treat using traditional cancer therapies.
In the past, researchers injected the cancer-killing protein TNF-related apoptosis inducing ligand (TRAIL) directly into the bloodstream to treat solid tumors. But due to its short half-life in the bloodstream, circulating at full-strength for mere minutes, TRAIL performed poorly on its own.
Next, attempts to bring TRAIL into more efficient contact with cancer cells in the blood combined it with an adhesion protein called e-selectin on the surface of a medical device that would filter and kill the cells. But for practical reasons, the researchers moved on to a method that placed both proteins on the surface of a nano-particle and injected it directly into the bloodstream like a drug.
Michael King, professor of biomedical engineering at Cornell University and co-author on the study, says, “During different iterations, we turned the geometry inside out. Instead of coating a device surface [with blood], we’ve taken a nano-device and sent it to the cells where they are.”
Through a physical phenomenon called margination, red blood cells flow down the middle of blood vessels while white blood cells and cancer cells are forced to congregate near each other along the vessel walls.
Like white blood cells, cancer cells roll along the walls of blood vessels. When TRAIL is injected into the blood along with e-selectin, it adheres to the surface of white blood cells. Any time one of these altered white blood cells bumps into a cancer cell, it’s likely that the cancer cell will die within a few hours, King says. Cancer cells in the blood find themselves surrounded by toxic surfaces.
King and his colleagues tested the current research model on human blood in vitro and mouse blood in circulation. To get to the clinic, the next steps would involve demonstrating the approach in more elaborate models of metastasis. A spin-off project involves coating lymphocytes with the TRAIL protein to tailor the therapy for the lymphatic system.
“Our hope is that if the approach continues to behave as successfully as it has so far, down the road, it could change the way metastatic cancers are treated,” King says. “Metastasis is responsible for over 90 percent of cancer deaths. We see this as the key to addressing that problem.”