Engineering Red Blood Cells as Activating Antigen Carriers
Red Blood Cells - The Perfect Carrier to Target the Immune System
With the rapid development of stem cells, gene editing and other technologies, red blood cell therapy technology has developed rapidly. Compared to other cell therapies, red blood cells have many advantages such as natural biocompatibility, high-throughput loading, low immunogenicity, complete biodegradability, long cycle times (120 days), and non-nucleation and non-cancer.
In addition to transporting oxygen, red blood cells interact very closely with the immune system, and together with the delivery of appropriate drugs, they can systematically affect the innate and adaptive immune systems. This natural property makes red blood cells an ideal drug delivery vehicle, providing a broad application prospect for medical research and treatment.
Red Blood Cell Therapy Technology Platform
This technique uses the physical extrusion of adult erythrocytes by osmotic pressure or microfluidic contraction to temporarily destroy the cell membrane, and then reseal the membrane after the drug has diffused into the cytoplasm.
Method
|
Effect
|
Limitation
|
Physical methods
|
The drug diffuses through the cell membrane to the cytoplasm
|
Disruption of the membrane structure of red blood cells
|
-
Genetically Engineering Technology
This technology mainly uses the differentiation of hematopoietic or pluripotent stem cells to obtain mature red blood cells, and the target protein gene is introduced and expressed through lentiviral vectors during the differentiation process.
Method
|
Effect
|
Limitation
|
Genetic engineering
|
Induction of hematopoietic or pluripotent stem cell differentiation
|
The cycle is more than 20 days and the price is expensive
|
-
Activating Antigen Carriers Technology
This technique uses ovalbumin, an antigenic protein that causes mild immune responses, to coat polystyrene carboxylate to produce nanoparticles that attach to red blood cells, so that the antigen adheres firmly enough to red blood cells. Subsequently, by reducing lung uptake, red blood cells are allowed to transport the drug to the spleen. When the ratio of nanoparticles to red blood cells is 300:1, red blood cells are able to quickly deliver drugs to the spleen while resisting clearance by the lungs.
Fig.2 Schematic diagram of red blood cells as activated antigen carrier engineering.1
We are here to share with you the latest cutting-edge research on this technology to help you better understand!
Published Data
-
The technique induces a higher serum protein-specific immune response.
Fig.3 Red blood cells act as carriers to present antigens to produce the immune response process.
After the nanoparticles were delivered to the spleen, mice were injected with red blood cells loaded with nanoparticles once a week for three weeks, and then their splenocytes were analyzed to assess whether the antigen on the surface of the nanoparticles could induce an immune response. The results showed that mice in the treatment group showed 8-fold and 2.2-fold more T cells that had undergone antigen compared to mice given "free" nanoparticles or untreated.
Fig.4 Immune response to nanoparticles delivered to the spleen.1
-
This technique significantly lengthens the index of the tumor, thereby increasing the chances of therapeutic intervention with other strategies.
Mice were given prophylactic injections for three weeks and then inoculated with ovalbumin-expressing lymphoma cells on the surface. Compared to the control and free nanoparticle groups, tumors in mice that received red blood cell-carrying antigens grew about 3 times slower and had a lower number of surviving cancer cells.
Fig.5 Immunotherapy of nanoparticles carried by erythrocytes.1
Based on the unique innate immune function of red blood cells, which capture certain pathogens in the blood. Creative Biolabs has developed a method for the delivery of vaccine nanoparticles to the spleen using red blood cells to prevent and inhibit tumor growth. If you are interested in this technology, you can always feel free to contact us.
Reference
-
Ukidve, Anvay.; et al. "Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function." Proceedings of the National Academy of Sciences of the United States of America. 117,30 (2020): 17727-17736.
For Research Use Only | Not For Clinical Use