The objective of the TregTherapeutics tolerogenic vaccine is to reverse the inflammatory T cell immune attack in demyelinating lesions of an MS patient, and subsequently, to create an anti-inflammatory tolerogenic response within that patient.
The vaccine is comprised of a tolerogenic cytokine and neuro-antigenic peptides. These components are electrostatically linked in an alum gel base and the formulation is injected subcutaneously. The cytokine utilized in such a manner induces a tolerogenic phenotype within antigen presenting cells (APCs), such as dendritic cells (DC), located in the subcutaneous tissue. The cytokine binds to its receptor on DCs, thus initiating a toleragenic cascade that results in subsequent preferential polarization of its cognate T cell into the FOX3P phenotype.
Concurrent with the action of the cytokine, the peptides are internalized by those same dendritic cells; these are processed and then arranged for presentation on MHC II molecules upon the surface of the cell. These activated DCs then travel to the draining lymph nodes where they come into contact with naive Tcells. When a cognate T cell receptor (TCR) is located, that Tcell, because of the influence of the tolerogenic cytokine previously described, is induced to become a FOXP3 Treg. This cell line is then clonally selected and expanded.
Instead of propagating pro-inflammatory T helper cells, as is the normal response of successful antigen presentation to a cognate Tcell, Teffector cells now undergo anergy and apoptosis. As stated, CD4+ CD25+, FOXP3+ Treg cells are clonally selected and their population expanded. The dynamic between declining T1 and T17 helper cells and the propagation of antigen-specific immunosuppressive Treg cell population reestablishes normal homeostasis, thus alleviating the pathogenic immune response. Tolerogenic memory T cells, created as part of this process, provide long-term recognition of pathologic neuropeptides as “self,” in lieu of the inflammatory reactions associated with the typical immune response in MS patients. The goal of the therapy is to end demyelination and other destructive neuropathological processes by reeducating the immune system to discriminate between self and non-self; thus, homeostatis is reestablished and long-term maintenance is accommodated by a robust population of antigen-specific memory Tregs in the CNS dedicated to self-tolerance.