Dendritic cell vaccines are becoming an important part of the immunotherapy toolkit for a wide range of diseases, including cancer, infectious disease, and autoimmunity. Dendritic cells are potent antigen presenting cells that can either stimulate or suppress immune response depending on their maturation state. By targeting key myelin protein to immature dermal dendritic cells, a group of researchers, including the laboratory of Gerard Zurawski, PhD, director of the Center for Biotechnology in the Baylor Scott & White Research Institute, part of Baylor Scott & White Health, have shown promising pre-clinical results for a candidate dendritic cell vaccine against demyelinating diseases.
Their recent manuscript, published in The Lancet EBioMedicine in September 2019, provides proof-of-principle that a dendritic cell vaccine can reduce autoimmunity in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), which is a primate model system for studying inflammatory demyelinating diseases. This work suggests that the vaccine could move forward to human trials.
Acute demyelinating diseases are a suite of debilitating neurological conditions. Although multiple sclerosis is the most well-studied demyelinating disease, there are other related disorders that rely on the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) and respond poorly to therapies targeted at multiple sclerosis. They include acute disseminated encephalomyelitis, optic neuritis, and neuromyelitis optica spectrum disorder. By strengthening immune tolerance to MOG, it is possible that these demyelinating diseases can be cured.
The team took advantage of the insight that immature dermal dendritic cells can promote immune tolerance. The tolerogenic DC-asialoglycoprotein receptor (DC-ASGPR) allows antigens to enter dendritic cells and be processed for presentation to T cells. Therefore, they created an antibody to DC-ASGPR that was attached to the MOG protein (anti-DC-ASGPR-MOG), which allowed the MOG protein to be processed and presented to T cells to induce immune tolerance.
They found that exposure to anti-DC-ASGPR-MOG prevented the appearance of behavioral and neurological deficits associated with EAE. Anti-DC-ASGPR-MOG also suppressed immune activation, including reducing CD4+ T cell activation and suppressing proinflammatory cytokine production. In addition, the treatment induced a population of circulating MOG-specific regulatory T lymphocytes and induced the cytokine TGF-beta, all of which support existing models for mechanisms of preventing autoimmunity.
Development of the immunotherapeutic products was supported by Baylor Scott & White Healthcare system funding. Members of the research team are also inventors on a patent that is pending for the use of DC-ASGPR targeting immunotherapeutics in demyelinating diseases. The Transfer Technology Office at Baylor Scott & White Research Institute collaborates with inventors throughout the discovery and development process to evaluate, patent, market, and manage the licenses for technology developed through BSWRI. They serve as a single point of contact for innovations across the Baylor Scott & White system, thereby creating efficient workflows.
