Red blood cells do more than shuttle oxygen from our lungs to our organs: they also help the body fight off infections by capturing pathogens on their surfaces, neutralizing them, and presenting them to immune cells in the spleen and liver.
A team of researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) has harnessed this innate ability to build a platform technology that uses red blood cells to deliver antigens to antigen-presenting cells (APCs) in the spleen, generating an immune response.
This approach successfully slowed the growth of cancerous tumors in mice, and could also be used as a biocompatible adjuvant for a variety of vaccines. The technology, called Erythrocyte-Driven Immune Targeting (EDIT), is reported this week in PNAS.
“The spleen is one of the best organs in the body to target when generating an immune response, because it is one of the few organs where red and white blood cells naturally interact,” said senior author Samir Mitragotri, a Wyss Core Faculty member who is also the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS. “Red blood cells’ innate ability to transfer attached pathogens to immune cells has only recently been discovered, and this study unlocks the door to an exciting array of future developments in the field of using human cells for disease treatment and prevention.”
A ‘check me out’ signal
Using red blood cells as delivery vehicles for drugs is not a new idea, but the vast majority of existing technologies target the lungs, because their dense network of capillaries causes cargoes to shear off of red blood cells as they squeeze through the tiny vessels. Mitragotri’s research team first needed to figure out how to get antigens to stick to red blood cells strongly enough to resist shearing off and reach the spleen.
They coated polystyrene nanoparticles with ovalbumin, an antigenic protein known to cause a mild immune response, then incubated them with mouse red blood cells. The ratio of 300 nanoparticles per blood cell resulted in the greatest number of nanoparticles bound to the cells, retention of about 80 percent of the nanoparticles when the cells were exposed to the shear stress found in lung capillaries, and moderate expression of a lipid molecule called phosphatidyl serine (PS) on the cells’ membranes.