PNAS: A new generation of cancer vaccines is hidden in the blood.

Red blood cells not only deliver oxygen from the lungs to organs, but also capture pathogens on their surface and then pass them on to immune cells in the spleen and liver to help the body fight infection.
A team of researchers at Harvard University used this innogeneant ability of red blood cells to build a platform technology called Erythrocyte-Driven Targeting (EDIT), which delivers antigens to antigen delivery cells in the spleen, producing an immune response.
this method can not only successfully slow the growth of cancerous tumors in mice, but can also be used as a bio-compatible admix for a variety of vaccines.
findings were published July 14 in PNAS.
photo source: PNAS "The spleen is one of the few organs in which red and white blood cells interact naturally.
the discovery that red blood cells have been found to transfer attached pathogens to immune cells, the study opens the door to a series of breakthroughs in disease treatment and prevention using human cells.
," said Dr. Samir Mitragotri, the author of the paper.
is not a new idea to use red blood cells as a drug delivery tool, but most of the organs targeted by existing technology are the lungs, where a dense network of capillaries allows the drug to be released as red blood cells pass through narrow blood vessels.
Mitragotri's team first needed to figure out how to make antigens stick firmly to red blood cells, enough to resist the shear stress of blood vessels and reach the spleen.
the researchers wrapped the egg white protein, an antigen protein that causes a mild immune response, with polystyrene nanoparticles, which were then incubated with mouse red blood cells, up to a maximum of 300 nanometers per red blood cell. Particles, when red blood cells are exposed to shear stress in the capillaries of the lungs, the retention rate of nanoparticles is about 80%, and the lipid molecule phosphatidyl serine (phosphatidyl serine, PS) on the cell membrane is moderately expressed.
" high levels of phosphatidylsine on red blood cells are actually a 'eat me' signal, which causes red blood cells under pressure or damage to be digested by the spleen.
We hope that lower levels of phosphatidylsine will temporarily signal 'check me out' to the spleen antigen delivery cells, which will then ingest nanoparticles encased in antigen encases on red blood cells without the red blood cells themselves being destroyed.
," said first author Anvay Ukidve.
to test this hypothesis, the team injected red blood cells containing nanoparticles into mice to track the accumulation of nanoparticles in the body.
20 minutes after the injection, it was found that more than 99 percent of the nanoparticles in the mice's blood had been removed and that there were more nanoparticles in the spleen than in the lungs (below).
, the accumulation of nanoparticles in the spleen lasts up to 24 hours, and the number of such EDIT red blood cells in the blood circulation remains the same.
suggests that red blood cells have successfully delivered nanoparticles to the spleen without destroying themselves.
image source: PNAS Researchers then assessed whether antigens on the surface of nanoparticles induced an immune response.
mice were injected with EDIT red blood cells once a week for three weeks.
After analyzing the spleen cells in mice, the researchers found that the T-cells in the treated mice showed that the ovum protein antigens were 8 times and 2.2 times higher than 8 times injected with free nanoparticles or unprocessed mice, respectively, and that after EDIT injection treatment, the mice produced more antibodies to the targeted egg white protein in their blood (below).
Photo Source: PNAS To study whether EDIT-induced immune responses have the potential to prevent or treat disease, the team repeatedly pre-injected mice with EDIT for three weeks before inoculation of lymphoma cells that surface expression of egg white protein.
results showed that mice receiving IT grew about three times slower than the control group and the free nanoparticle group, and had fewer cancer cells alive.
results significantly increased the window period available to treat tumors prior to mouse death (below).
photo source: Zongmin Zhao, lead author of the PNAS paper, argues that EDIT is essentially a vaccine platform without adulations.
the longer time it takes to develop vaccines today, partly because foreign adrenasts delivered with antigens in each new vaccine must be fully clinically safe to test.
red blood cells have been safely lost to patients for centuries, and this ability to enhance the immune response of red blood cells can make them safe alternatives to foreign adulents, thereby increasing the effectiveness and speed of vaccine production.
's research team is continuing to delve into how antigen-presenting cells in the spleen produce immune responses to antigens delivered by targeted EDIT, and plan to explore the best clinical environment for this technology by testing IT with antigens other than egg white proteins.
" human body is a treasure trove of high-quality solutions to medical problems, and while we have come a long way in understanding these mechanisms, they are still in the early stages of using them to improve human life and quality of life.
this study is an exciting step toward that goal and could dramatically change the way patients' immune responses are regulated.
, " says Dr. Donald Ingber, founder of the Wyss Institute.
: 1 s Anvay Ukidve el al., Erythrocyte-driven immunization via biomimicry of of their natural antigen-presenting function (Source: PNAS) 2 s Better vaccines are in our blood (Source: Harvard University website)