Monoclonal antibodies in the treatment of multiple sclerosis: emergence of B‐cell‐targeted therapies

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease-modifying therapies have emerged, including monoclonal antibodies (mAbs) that provide highly targeted therapies with greater efficacy than platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials and renewed interest in the mechanism of B cell-depleting therapies to ameliorate relapse activity and progression in MS. Here, we review the mechanisms of action and clinical evidence of approved and emerging mAbs, with a focus on B cell-targeted therapies.

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

“…Some B cells undergo a proliferative phase and develop into plasma cells, which secrete myelin-specific antibodies. These antibodies are highly structurespecific and can lead to functional impairment and lesion evolvement (Nguyen et al, 2017). The intrathecal oligomeric myelin-specific antibodies have been used to diagnose MS for a long time (Nguyen et al, 2017).…”

“…These antibodies are highly structurespecific and can lead to functional impairment and lesion evolvement (Nguyen et al, 2017). The intrathecal oligomeric myelin-specific antibodies have been used to diagnose MS for a long time (Nguyen et al, 2017). In addition to producing antibodies, B cells also exert their effector functions via cytokine secretion.…”

Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis

“…In MS patients, a portion of activated B cells act as APCs, presenting myelin antigens to CD4+ T cells and improving Th1 and Th17 responses [183][184][185]. Plasma cells produce myelin specific antibodies that not only cause functional myelin impairment, but also form oligoclonal bands (OCBs) within the CNS and peripheral blood [186]. The detection of OCBs from cerebrospinal fluid are used to diagnose MS with high sensitivity [187,188].…”

Signaling pathways and therapeutic perspectives related to environmental factors associated with multiple sclerosis

“…Polyclonal antibody therapies inhibit cell‐mediated immune reactions by causing general immunosuppression, albeit not commonly used in MS due to high toxicity (Walker, Hoehn, & Kashiwagi, ). On the other hand, numerous monoclonal antibodies including Natalizumab, Alemtuzumab and Daclizumab have proven effective in early RRMS(Nguyen, Gresle, Marshall, Butzkueven, & Field, ). In addition, three emerging monoclonal antibodies against CD20‐positive B cells (rituximab, ocrelizumab, and ofatumumab) have shown overall promising effects in clinical phase II and III trials (Abbruzzese et al, ; Reff et al, ; Stashenko, Nadler, Hardy, & Schlossman, ).…”