A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy.

Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers.

A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial.

Introduction: Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS.

Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner.

Although the global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, there are currently no specific and highly efficient drugs for COVID-19 available, particularly in severe cases. Recent findings demonstrate that severe COVID-19 disease that requires hospitalization is associated with the hyperactivation of CD4 and CD8 T cell subsets. In this study, we aimed to counteract this high inflammatory state by inducing T-cell hyporesponsiveness in a SARS-CoV-2-specific manner using tolerogenic dendritic cells (tolDC).

Impaired B Cell Expression of the Inhibitory Fcγ Receptor IIB in Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disease in which pathogenic immunoglobulin G antibodies bind to acetylcholine receptors (or to functionally related molecules at the neuromuscular junction). B cell expression of the inhibitory immunoglobulin G receptor, Fc-gamma receptor (FcγR) IIB, maintains peripheral immune tolerance, and its absence renders B cells hyperresponsive to autoantigen. Here, we report that FcγRIIB expression levels are substantially reduced in B lineage cells derived from immunotherapy-naïve patients with acetylcholine receptor antibody-positive early-onset MG.

Neuromyelitis Optica Spectrum Disorders in Africa: A Systematic Review.

Background And Objectives: Neuromyelitis optica (NMO) is a CNS inflammatory disease that predominantly affects the optic nerves and the spinal cord. It is more frequent in Asian and African populations than in European ones. Data on epidemiology, clinical presentation, additional investigations, and treatment in the African continent are scarce.

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD.

Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clinical trials or have been used as rescue treatment in treatment-refractory cases.

Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies.

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS.

Antigen-Specific Treatment Modalities in MS: The Past, the Present, and the Future.

Antigen-specific therapy for multiple sclerosis may lead to a more effective therapy by induction of tolerance to a wide range of myelin-derived antigens without hampering the normal surveillance and effector function of the immune system. Numerous attempts to restore tolerance toward myelin-derived antigens have been made over the past decades, both in animal models of multiple sclerosis and in clinical trials for multiple sclerosis patients. In this review, we will give an overview of the current approaches for antigen-specific therapy that are in clinical development for multiple sclerosis as well provide an insight into the challenges for future antigen-specific treatment strategies for multiple sclerosis.

HLA Class II Genotype Does Not Affect the Myelin Responsiveness of Multiple Sclerosis Patients.

Background: When aiming to restore myelin tolerance using antigen-specific treatment approaches in MS, the wide variety of myelin-derived antigens towards which immune responses are targeted in multiple sclerosis (MS) patients needs to be taken into account. Uncertainty remains as to whether the myelin reactivity pattern of a specific MS patient can be predicted based upon the human leukocyte antigen (HLA) class II haplotype of the patient.

Methods: In this study, we analyzed the reactivity towards myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) and proteolipid protein (PLP) peptides using direct interferon (IFN)-γ enzyme-linked immune absorbent spot (ELISPOT).

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration.

Introduction: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains.

Clinical and immunological control of experimental autoimmune encephalomyelitis by tolerogenic dendritic cells loaded with MOG-encoding mRNA.

Background: Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s), followed by a cascade of epitope spreading, which are both strongly patient-dependent.

Shuttling Tolerogenic Dendritic Cells across the Blood-Brain Barrier the Introduction of C-C Chemokine Receptor 5 Expression Using Messenger RNA Electroporation.

The use of tolerance-inducing dendritic cells (tolDCs) has been proven to be safe and well tolerated in the treatment of autoimmune diseases. Nevertheless, several challenges remain, including finding ways to facilitate the migration of cell therapeutic products to lymph nodes, and the site of inflammation. In the treatment of neuroinflammatory diseases, such as multiple sclerosis (MS), the blood-brain barrier (BBB) represents a major obstacle to the delivery of therapeutic agents to the inflamed central nervous system (CNS).

GMP-Grade mRNA Electroporation of Dendritic Cells for Clinical Use.

mRNA-electroporated dendritic cells (DC) are demonstrating clinical benefit in patients in many therapeutic areas, including cancer and infectious diseases. According to current good manufacturing guidelines, cell-based medicinal products have to be defined for identity, purity, potency, stability, and viability. In order to comply with the directives and guidelines defined by the regulatory authorities, we report here a standardized and reproducible method for the manufacturing of clinical-grade mRNA-transfected DC.