Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur
with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical
transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction
treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies
are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific
peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host
immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in
regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists,
transplantation immunologists and materials scientists.
Four professors leading research groups at the Faculty of Life Sciences have been awarded an ADVANCED GRANT 2013 from the European Research Council (ERC), in recognition of their outstanding research performed at the EPFL…
…Jeffrey Hubbell, head of the Laboratory of Regenerative Medicine & Pharmacobiology (Merck Serono Chair in Drug Delivery), for his research on Engineering Cytokines for Super-Affinity Binding to Matrix in Regenerative Medicine....
Symptoms of an autoimmune disease disappeared after a team of scientists retrained white blood cells using a specially engineered protein. This method is extremely promising for treating diseases such as type I diabetes and multiple sclerosis.
How can the immune system be reprogrammed once it starts to attack its own body? EPFL scientists retrained white blood cells responsible for type I diabetes, a common autoimmune disease. Using a modified protein, they precisely targeted these white blood cells (T-lymphocytes, or T-cells) that were attacking pancreatic cells and causing the disease. When tested on laboratory mice, the therapy eliminated all signs of the pathology. This same method could be extremely promising in treating multiple sclerosis as well. The scientists have just launched a start-up Anokion SA on the Lausanne campus, and are planning to conduct clinical trials within the next two years. Their discovery has been published in the journal PNAS (Proceedings of the National Academy of Science).
To retrain the rebellious white blood cells, the researchers began with a relatively simple observation. Every day, thousands of our cells die. Each time a cell expires, it sends out a message to the immune system. If the death is caused by trauma, such as inflammation, the message tends to stimulate white blood cells to become aggressive. But if the cell dies a programmed death at the end of its natural life cycle, it sends out a calming signal.
In the human body there is a type of cell that dies off profusely, at the order of 200 billion per day: red blood cells. There are as many calming signals transmitted daily to the immune system.
The scientists therefore attached the pancreatic protein targeted by T-cells in type I diabetes to red blood cells. “Our idea was that by associating the protein under attack to a soothing event, like the programmed death of red blood cells, we would reduce the intensity of the immune response,” explains Jeffrey Hubbell, co-author of the study. To do this, the researchers opted for state-of-the-art bioengineering: the protein, equipped, with a hook of molecular size, is able to attach itself to red blood cells. Billions of these were manufactured and then simply injected into the body....
Engineering antigens for in situ erythrocyte binding induces T-cell deletion.
“Antigens derived from apoptotic cell debris can drive clonal T-cell deletion or anergy, and antigens chemically coupled ex vivo to apoptotic cell surfaces have been shown correspondingly to induce tolerance on infusion. Reasoning that a large number of erythrocytes become apoptotic (eryptotic) and are cleared each day, the group of Prof. Jeffrey Alan Hubbell (Merck Serono Chair in Drug Delivery) engineered two different antigen constructs to target the antigen to erythrocyte cell surfaces after i.v. injection, one using a conjugate with an erythrocyte-binding peptide and another using a fusion with an antibody fragment, both targeting the erythrocyte-specific cell surface marker glycophorin A. They report a translatable modular biomolecular approach with which to engineer antigens for targeted binding to erythrocyte cell surfaces to induce antigen-specific CD4+ and CD8+ T-cell deletion toward exogenous antigens and autoantigens.”...
Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination.
Disulfide-linked nanoparticle-antigen conjugates could be useful for creating vaccines that elicit pulmonary cytotoxic T cell responses. As shown by the groups of Prof. Jeffrey Hubbell (LMRP – Merck Serono Chair in Drug Delivery) and Prof. Melody Swartz (LLCB – Laboratory of Lymphatic and Cancer Bioengineering), intranasal delivery of a model antigen linked to a nanoparticle increased Cd8+ T cell responses and improved protection against an engineered influenza strain compared with unconjugated antigen in mice. Next steps will include testing the vaccine in additional pulmonary indications, including lung cancer and tuberculosis....