Multiple myeloma is an incurable bone marrow cancer that kills over 100,000 people every year. Known for its quick and deadly spread, this disease is one of the most challenging to address. As these cancer cells move through different parts of the body, they mutate, outpacing possible treatments. People diagnosed with severe multiple myeloma that is resistant to chemotherapy typically survive for only three to six months. Innovative therapies are desperately needed to prevent the spread of this disease and provide a fighting chance for those who suffer from it.
Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering (BE), and Christian Figueroa-Espada, doctoral student in BE at the University of Pennsylvania School of Engineering and Applied Science, created an RNA nanoparticle therapy that makes it impossible for multiple myeloma to move and mutate. The treatment, described in their study published in PNAS, turns off a cancer-attracting function in blood vessels, disabling the pathways through which multiple myeloma cells travel.
By shutting down this “chemical GPS” that induces the migration of cancer cells, the team’s therapy stops the spread of multiple myeloma, helping to eliminate it altogether.
Endothelial cells, those that line blood vessels, produce a protein we need to survive. This protein, CyPA, is responsible for folding and transporting other proteins. It also activates T-cell responses when we get sick.
However, when multiple myeloma is present, endothelial cells overexpress CyPA and secrete it into the blood vessels where its functions become malignant. Here, CyPA is a chemo-attractant, meaning it pulls multiple myeloma cells from the bone marrow into the blood vessels where they travel quickly to other bones in the body.
“To stop the spread, we aimed to turn off this function of CyPA using RNA therapy, targeting the microenvironment of the cancer instead of the cancer cell itself,” says Mitchell. “But getting nucleic acids into the marrow was challenging due to the complex biological barriers.”
This story is by Melissa Pappas. Read more at Penn Engineering Today.