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

Text . . . Li Yuan red blood cells not only transport oxygen from the lungs to the organs, but also capture pathogens on their surface, neutralizing them and passing them to immune cells in the spleen and liver, helping the body fight infection.
a team of researchers at Harvard University used this innate capability of red blood cells to build a platform technology called Erythrocyte-Driven Immune Targeting (EDIT), which delivers antigens to antigen-presented cells in the spleen, producing an immune response.
this method not only successfully slows the growth of cancerous tumors in mice, but can also be used as a biocompatible adjugate dissociated for a variety of vaccines.
related findings were published July 14 in PNAS.
photo source: PNAS"spleen is one of the few organs where red blood cells interact naturally with white blood cells.
red blood cells have been found to be able to transfer attached pathogens to immune cells, and on the basis of this finding, the study opens the door to a series of future breakthroughs in the treatment and prevention of disease using human cells.
," said Dr. Samir Mitragotri, the paper's communications author.
using red blood cells as a drug delivery tool is not a new idea, but the vast majority of the target organs of the current technology are the lungs, because the dense network of capillaries in the lungs allows the drug to be released from it as red blood cells pass through narrow blood vessels.
Dr. Mitragotri's team first needed to figure out how to bind the antigen firmly to the red blood cells, enough to resist the shear stress of the blood vessels and reach the spleen.
researchers packed polystyrene nanoparticles with egg-clearing proteins, an antigen that cause a mild immune response, and then incubated the packs with mouse red blood cells, up to 300 nanoparticles per red cell, with the retention rate of the nanoparticles at about 80% when red cells were exposed to shearing stress in the capillaries of the lungs, and the lipid molecule sphinylliate in the cell membranewas.
"high levels of phosphatidylseline on red blood cells are actually a 'eat me' signal, which causes red blood cells under stress or damage to be digested by the spleen.
we hope that lower levels of phosphatidylsethane will temporarily signal the spleen antigen-presentation cells 'check me out', and then the antigen-presentation cells will ingest nanoparticles of antigen encapsulation on red blood cells, while the red blood cells themselves will not be destroyed.
," said first author Anvay Ukidve. to test this hypothesis
, the team injected red blood cells with nanoparticles into mice to track their accumulation in the body.
20 minutes after injection, more than 99 percent of the nanoparticles in the mice's blood were removed and more nanoparticles in the spleen than in the lungs (below).
, the build-up of nanoparticles in the spleen lasts up to 24 hours, and the number of the EDIT red blood cells in the blood circulation remains the same.
this shows that red blood cells have successfully delivered nanoparticles to the spleen and are not destroyed themselves.
photo source: PNAS later researchers 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 of mice, the researchers found that the T cells of the mice treated showed that the t cells of the egg-clearing protein antigen were 8 times and 2.2 times higher than those injected with free nanoparticles or untreated mice, respectively, and that the mice had more antibodies to target the egg-clearing 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 repeated three-week EDIT pre-injections in mice before inoculating lymphoma cells that surface-to-surface proteins.
results showed that the mice receiving EDIT had tumorgrowth about three times slower than that of the control group and the free nanoparticle group, and that fewer cancer cells survived.
this result significantly increased the window period that can be used to treat tumors before the mice die (below).
picture source: Zongmin Zhao, lead author of the PNAS paper, argues that EDIT is essentially a adjugate-free vaccine platform.
the time it takes to develop vaccines today, in part because the foreign adjuvants delivered with antigens in each new vaccine must undergo comprehensive clinical safety trials.
and red blood cells have been safely lost to patients for centuries, and the ability of red blood cells to enhance the immune response can make them safe alternatives to foreign adjacency, thereby increasing vaccine effectiveness and faster production.
research team is continuing to conduct in-depth exploration to understand exactly how spleen antigen presentation cells produce an immune response that targets edIT-delivered antigens, and plans to test EDIT with other antigens other than egg-clearing proteins to explore the best clinical settings for this technology.
"The human body is a treasure trove of quality solutions to medical problems, and while we have come a long way to understand these mechanisms, we are still in the early stages of using it to improve human life expectancy and quality of life."
this study is an exciting step toward this goal and could dramatically change the way patients respond to immunity.
," said Dr. Donald Ingber, founder of the Wyss Institute.
References: 1?Anvay Ukidve el al., Erythrocyte-driven immunization-driven via bio-photography of their natural antigen-presenting function (Source: PNAS) 2 s betters vaccine are in our sour blood (Source: Harvard University Website)