Scientists are developing a novel vaccination method to deliver antigens to the spleen. They have shown in mice that it can generate an immune response which can successfully slow cancer growth.
A team led by Dr Samir Mitragotri from Harvard Medical School, USA, created new technology they call Erythrocyte-Driven Immune Targeting (EDIT). This method harnesses red blood cells to deliver ‘hitchhiking’ antigens attached to nanoparticles to antigen-presenting cells in the spleen.
Details appeared in the journal PNAS. Previous experiments have used red blood cells to deliver drugs to the lungs. However, the team wanted to ensure that the antigens reached the spleen instead, one of the few organs where red and white blood cells naturally interact.
To do so, the team coated polystyrene nanoparticles with the protein ovalbumin, then incubated them with mouse red blood cells at a ratio of 300 nanoparticles per blood cell. They found that this ratio ensured more nanoparticles were delivered to the spleen than the lungs, while also keeping the expression of a molecule called phosphatidyl serine low on the cells’ membranes.
Joint first author, Dr Anvay Ukidve, explained: “A high level of phosphatidyl serine on red blood cells is essentially an ‘eat me’ signal that causes them to be digested by the spleen when they are stressed or damaged, which we wanted to avoid.”
Red blood cells efficiently delivered the nanoparticles to antigen presenting cells in the spleen. In experiments with mice, the researchers showed that this generated a stronger immune response compared to ‘free’ nanoparticles, generating more antibodies against ovalbumin.
The team finally tested the ability of EDIT to generate an immune response against lymphoma cells that express ovalbumin. They showed that EDIT slowed tumour growth more efficiently than vaccinating with free nanoparticles, delaying the progression of the disease in the mice.
Dr Mitragotri commented: “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.”
Ukidve A, Zhao Z, Fehnel A, Krishnan V, Pan DC, Gao Y, Mandal A, Muzykantov V, Mitragotri S (2020) “Erythrocyte-Driven Immunization via Biomimicry of their Natural Antigen Presenting Function.” PNAS, doi: 10.1073/pnas.2002880117
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