Adoptive T‐cell therapy targeting Epstein–Barr virus as a treatment for multiple sclerosis

Abstract

Emergence of a definitive link between Epstein-Barr virus (EBV) and multiple sclerosis has provided an impetus to develop immune-based therapies to target EBV-infected B cells. Initial studies with autologous EBV-specific T-cell therapy demonstrated that this therapy is safe with minimal side effects and more importantly multiple patients showed both symptomatic and objective neurological improvements including improved quality of life, reduction of fatigue and reduced intrathecal IgG production. These observations have been successfully extended to an 'off-the-shelf' allogeneic EBV-specific T-cell therapy manufactured using peripheral blood lymphocytes of healthy seropositive individuals. This adoptive immunotherapy has also been shown to be safe with encouraging clinical responses. Allogeneic EBV T-cell therapy overcomes some of the limitations of autologous therapy and can be rapidly delivered to patients with improved therapeutic potential.

Unraveling the Connection of Epstein–Barr Virus and Its Glycoprotein M146–157 Peptide with Neurological Ailments

“…The myelin basic protein (MBP) autoreactive T-cells also showed cross-reactivity against the EBV protein EBNA1 . Albeit of MBP, these cells showed cross-reactivity toward other host proteins such as anoctamin 2, α-crystallin B chain, and glial cell adhesion molecule (GlialCAM) . Cross-reactivity of antibodies toward GlialCAM and EBNA1 has shown their presence in the CSF of MS patients .…”

Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review

“…Hence, EBV reprograms naïve B-cells towards a developmental path comprising a proliferative state, a germinal center-like phenotype, and a memory B-cell phenotype. These developmental stages correspond to different viral gene programs called “latency profiles” [ 106 , 109 ]. The proliferative stage shows a so-called latency III profile, characterized by the expression of the proteins LMP1 and 2 and EBV nuclear antigens (EBNA) 1 to 6.…”

Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients

“…Genome wide association studies (GWAS) and transcriptome studies of MS patients have repeatedly indicated antiviral proteins as risk factors in disease occurrence and progression 5,34,35 . Clinical trials of T cell therapy specifically targeting EBV have even begun 36 with promising early results for both clinical improvement and decrease in EBV antibody titre.…”

“…Clinical trials of T cell therapy specifically targeting EBV have even begun 36 with promising early results for both clinical improvement and decrease in EBV antibody titre.…”