The therapeutic antibody anchored onto the red blood cell membrane (left) can bind to disease-causing antigens (right). Elsevier 2020
Researchers around the world are trying to modify red blood cells to carry antibody molecules to treat disease. Progress by a group based at Carnegie Mellon University in Pittsburgh, United States is reported in the journal Acta Biomaterialia.
Antibodies are protein molecules that are naturally produced by the immune system to bind to foreign microbes or diseased cells, provoking other aspects of the immune system to eliminate these targets. Attaching large quantities of selected antibodies to red blood cells, which transport oxygen around the body, could open up a revolutionary approach for assisting our natural immune responses. The cells would travel through blood, binding to and neutralising antigens – the specific molecules associated with causing disease.
“We were able to attach over 100,000 antibody molecules to the surface of one red blood cell without harming the cell or losing the functionality of the antibody,” says Paige Smith of the research team. Smith is working on the project as a PhD student in the research group led by Alan Russell.
Using selected antibodies to treat disease has been used to some extent for many years, but the Carnegie Mellon team explain that three key challenges are hindering progress. Antibodies don’t persist very long when administered directly into the body, soluble complexes between the antibodies and their targets can cause problematic disruption of the immune response, and the immune system can sometimes generate new antibodies that target and bind to the antibodies being used as treatments.
Several research groups are now exploring the hope that using red blood cells to carry and display therapeutic antibodies might overcome all or some of these challenges, each using different systems and at different stages of development. “We see our delivery system being used for a wide spectrum of antibody-based therapies,” says Smith, emphasising its potential versatility.
Their approach is based on the ability of a protein found on bacterial cells to carry and display antibody molecules. The team attached this protein to red blood cells using an anchoring linker composed of polyethylene glycol. “This enables the attachment of virtually any antibody to the cell surface,” says Smith.
To prove the feasibility of the concept they attached an antibody called anti-tumour necrosis factor, which is used to treat various autoimmune diseases such as rheumatoid arthritis.
The team has shown that the engineered cells are stable in simple solutions for at least 60 days, and in blood serum for at least 42 days, but in this early stage of development they have not yet been tested in animal trials, either for stability or ability to treat disease. That is the next step, while also widening the procedure to attach other antibodies and hopefully target many diseases.
“I have become passionate about the work as it weaves together chemistry, biology, and material science to solve real-world problems,” says Smith. “As I continue to work on my PhD, I’m excited to explore how we can adapt our system for different types of bio-therapeutics.”
Article details:
Russell, A. J. et al: “Erythrocytes as carriers of immunoglobulin-based therapeutics,” Acta Biomaterialia (2020)
Acta Biomaterialia is part of the family of Acta Materialia Inc journals, which also includes Materialia, Acta Materialia and Scripta Materialia.