Researchers at Michigan State University in East Lansing were awarded nearly $2.6 million from the National Institutes of Health to create a breast cancer treatment that acts as a trojan horse.
The researchers are using nanoscopic particles to turn the body’s own cells into weapons that can fight tumor cells.
“We are developing a precision ‘Trojan Horse’ nanotherapy that treats breast cancer without the typical side effects,” says Bryan Smith, associate professor in MSU’s Biomedical Engineering Department and director of the Translational NanoImmunoEngineering, or T-NIE, lLab. “If we can show this is effective in animal models and bring it to humans, there is tremendous potential for cancer patients,” he said.
The research team is working to help the body’s immune system infiltrate tumors. The approach, which Smith is also deploying to fend off plaques that clog and damage arteries, is expected to minimize the collateral damage caused by related cancer therapies.
The group’s project focuses on macrophages, or cells that are part of the immune system that ingest and digest pathogens and other intruders. Many cancer cells, however, coat themselves with a protein known as CD47, which many of the body’s health cells use to tell macrophages to leave them alone.
“They call it the ‘don’t eat me’ molecule,” Smith says.
As breast cancer grows, the body recognizes a problem and sends macrophages to eat the cancer cells. However, CD47 keeps them from doing so.
Researchers are interested in drugs that can neutralize CD47; biotech company Gilead Sciences spent nearly $5 billion to acquire the startup company Forty Seven, which is investigating one such treatment.
Getting rid of all CD47 in the body, however, would cause healthy cells to become casualties.
“For example, red blood cells express high levels of CD47,” Smith says. “These drugs could lead to anemia.”
To fight this, Smith and his team are developing ultra-thin carbon tubes that naturally seek out macrophages and their cellular predecessors, which are called monocytes. The tiny tubes carry a chemical cargo that gives immune cells the order to disregard CD47, which the tubes release only after they’ve made it inside macrophages or monocytes that are drawn to tumors. The drug-loaded tubes arm the immune cells, helping launch a covert attack targeting breast cancer cells.
Preliminary work shows reduced side effects and unexpectedly proves more effective at taking down cancer cells than related treatments. The early work was done using cells cultured in petri dishes. The team will next study the therapy in animal models thanks to the NIH grant.
“The funded work to use nanoparticles as a selective therapy has potential to revolutionize therapy,” says Eran Andrechek, associate professor in the Department of Physiology, who is a grant co-investigator. “I’m excited to be collaborating on this project and am offering our expertise in preclinical models of breast cancer.”
Other researchers are from MSU, and one is from Stanford University. While the research focuses on breast cancer, the team thinks the strategy could work on many forms of cancer that use a CD47 defense.