Toby Lanser, BAS
Technical Research Associate I
Toby Black Lanser, Rafael Machado Rezende, Danielle Sydney Leserve, Christian Barro, Christian Gauthier
Research Category: Neurosciences
Multiple Sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS) characterized by demyelination of the brain and spinal cord. Driven by chronic inflammation and immune self-stimulation, this demyelination leads to, if untreated, irreversible clinical and cognitive decline. The nature of this pathology can be traced back to the immune system, notably self-reactive T, B, and myeloid cells which infiltrate the central nervous system. Modulating the immune system in MS has become a major focus of therapeutics in recent years, with the rise of immunomodulatory monoclonal antibodies (mAb) leading the way. Currently, only intravenous mAbs for MS are clinically approved, with the majority of their targets being B lymphocytes. Here, we investigate the effects of a nasal aCD3 mAb to target T cells in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Specifically, we analyze the transcriptomic differences of aCD3 and isotype control mouse T cells through single-cell RNA sequencing. The resulting differences elucidate how T-cell targeted mAbs modulate an inflammatory environment to dampen CNS autoreactive T cells and provide a view into potential new targets for cellular therapies in autoimmune disorders.
Multiple Sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS) characterized by demyelination of the brain and spinal cord. Driven by chronic inflammation and immune self-stimulation, this demyelination leads to, if untreated, irreversible clinical and cognitive decline. As an autoimmune disorder, the root cause of MS is engrained in an over-reactive immune system whose warped goal is to attack one’s own body. Taming this auto-reactive response has become the key in treating patients with MS. Recently, the use of monoclonal antibodies (mAbs) has brought promise to targeted cellular therapies. These mAbs, however, mainly target one specific cell type of the immune system and are all given by injections. Here, investigate how a novel nasal spray mAb aimed at targeting another cell type of the immune system tames the effects of MS at its immunological source in a mouse model. To clearly peer into these differences, we isolated and sequenced these individual cells at the RNA level. This RNA sequencing enables us to understand how the cells are reacting, individually, to our treatment in the context of MS.