B-cells

Immune B-cells that proliferate unchecked when infected by the Epstein-Barr virus (EBV) appear to increase the risk of relapses in patients with multiple sclerosis (MS), a mouse study suggests. The study, “Epstein Barr virus‐immortalized B lymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice,” was published…

Atara Biotherapeutics has enrolled a first patient in a clinical trial testing ATA188, its off-the-shelf T-cell immunotherapy for people with progressive forms of multiple sclerosis (MS). The Phase 1b trial (NCT03283826) follows promising safety and tolerability results from its open-label Phase 1a part, including a…

Australian scientists have discovered subsets of immune cells that differ between people who have multiple sclerosis (MS) and those who don’t. Because the prevalence of these cells correlates with autoimmune attacks, they represent potential targets for MS therapies. The study, “IgG3 + B…

Atara Biotherapeutics‘ cell-based therapy ATA188 is safe and well-tolerated in people with progressive forms of multiple sclerosis (MS), and induces a sustained reduction in disability in a dose-dependent manner, findings from the first part of a Phase 1 clinical trial show. ATA188 had an…

Ofatumumab (OMB157) elicits a strong and fast reduction in the levels of circulating immune cells in people with relapsing forms of multiple sclerosis (MS), effectively helping to stop disease activity, according to new data from the Phase 2 APLIOS trial. The medication was also found to be more…

NurOwn, believed to have neuroprotective and repairing effects, may also be able to curb the damaging immune responses that contribute to multiple sclerosis (MS) progression, a recent study found. This newly identified potential may extend the benefits of this cell-based therapy, its researchers believe. The findings were to be presented…

COVID-19 infection in a multiple sclerosis (MS) patient being treated with Ocrevus (ocrelizumab) — an immunosuppressive therapy — was not associated with any serious complications, a case study reports. This finding supports current suggestions that immunosuppressive therapies, by dampening immune and inflammatory responses, may help to protect…

The investigational anti-CD20 antibody ublituximab effectively depletes B-cells in people with relapsing forms of multiple sclerosis (MS), reducing the appearance of brain lesions and the risk of relapses, a study into clinical trial results suggests. Findings further suggest that the…

Using rituximab to prevent multiple sclerosis (MS) in people at risk or in patients still without motor symptoms, and continuing treatment as the disease develops, may be a promising way to avoid inflammation and myelin loss in the brain, a study in mice suggests. In an animal model of MS,…

The lack of a “chaperone” protein — called HLA-DO — that helps to protect the body against threats by presenting specific molecules (antigens) to immune cells to drive a response, promoted the development of a self-reactive immune system and autoimmune disease, according to a study in mice. Particularly, the work showed…

Monthly under-the-skin injections of Novartis’ investigational candidate ofatumumab show promise as a convenient, effective, and safe therapeutic option for people with relapsing multiple sclerosis (MS). Data from the ASCLEPIOS and APLIOS clinical trials showed that ofatumumab — currently under regulatory review for possible approval in the U.S. and Europe…

Using a patient-friendly autoinjector pen to take monthly doses of ofatumumab — an investigational B-cell therapy for relapsing multiple sclerosis (MS) — is bioequivalent to delivering it via a prefilled syringe, and would allow self-administration of the treatment at home, a study shows. Equal effects…

Treating people with relapsing-remitting multiple sclerosis (RRMS) for one year with the immune-modulating therapy Gilenya (fingolimod) reduced the numbers of antibody-producing B-cells and of T helper cells, a study finds.  While the…

People with multiple sclerosis (MS) have a more diverse set of immune cells in their cerebrospinal fluid (CSF), the fluid that bathes the central nervous system, but no such diversity is seen in their blood, a study reports. Instead, MS causes changes in the activation of immune cells in…

Mayzent (siponimod), an approved oral therapy for active secondary progressive multiple sclerosis (SPMS), promotes a more regulatory immune system, which may explain its added benefits for SPMS, new clinical data show. The study “Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis” was published in the…

Tysabri (natalizumab), an effective T-cell targeting treatment for multiple sclerosis (MS), seems to also promote the activation of pro-inflammatory immune B-cells in people with this disease, a study found. The study, “Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients,” was published in the…

Stopping the migration of immune B-cells through the blood-brain barrier by blocking ALCAM, a molecule linked to the progression of multiple sclerosis (MS), lessened disease severity in an MS mouse model, a new study shows. Details of the discovery were reported…

Editor’s note: This is the second story in a three-part report examining the question, “Is rituximab a reasonable alternative treatment for MS?”, which was a topic discussed at this year’s Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Here, we take an in-depth look…

Treatment for more than six years with Ocrevus (ocrelizumab) is linked to lower levels of blood antibodies among people with primary progressive multiple sclerosis (PPMS) and relapsing MS, but rates of serious infections also remain low, an analysis of data from three Phase 3 trials show. Dropping below a certain…

The loss of immune B-cells, and the resulting changes in the profile of immune T-cells, is a major mechanism of action for the beneficial effects seen with ublituximab treatment in multiple sclerosis (MS) patients, a study suggests. B-cells are a type of immune cell best known for producing…

Early, positive safety results from a Phase 1 trial testing a potential immunotherapy, ATA188, in people with progressive multiple sclerosis will be detailed at the 5th Congress of the European Academy of Neurology (EAN) late next month, its developer, Atara Biotherapeutics, announced. ATA188 is an investigational and “off-the-shelf”…

Treatment with Ocrevus (ocrelizumab) decreases the levels of neurofilament light chain (NfL) and immune B-cells in the serum and central nervous system of patients with relapsing multiple sclerosis (MS), according to results from a Phase 3 trial. The research, “Ocrelizumab treatment reduced levels of neurofilament light chain and…

This year’s John Dystel Prize for Multiple Sclerosis Research is being awarded to Anne H. Cross, a neurologist and MS chair in the department of neuroimmunology at  Washington University School of Medicine in St. Louis, for her research into the role of immune B-cells in multiple sclerosis attacks and new imaging…

Full results of a Phase 2 clinical trial testing TG Therapeutics’ lead candidate ublituximab (TG-1101) for relapsing multiple sclerosis (MS) showed that treatment for 48 weeks resulted in a marked reduction of brain and spinal cord lesions, an almost complete depletion of relapse-associated immune B-cells, and significantly halted disability…

Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, “Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients,” was published in the journal Cells. Autoreactive immune T-cells, which attack the body’s own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy is Genentech’s Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid — the liquid surrounding the brain and spinal cord — and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximab (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatment that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximab’s clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical School in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patients’ peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease for a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes — white blood cells that include T- and B-cells — and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cells’ fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. “Our results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,” the researchers wrote. “These findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,” they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.

Immune cells in the intestine may reduce neuroimflammation in multiple sclerosis (MS) patients, a pre-clinical study suggests. Moreover, the augmented number of these cells was sufficient to suppress brain inflammation in an MS mouse model. The findings were reported in the study “Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via…

Atara Biotherapeutics’ investigational ATA190, a cell therapy that wipes out immune B-cells infected with the Epstein-Barr virus (EBV), led to neurological improvements and reduced symptoms in patients with primary and secondary progressive multiple sclerosis (MS), a Phase 1 trial shows. The trial results were published in the Journal…

MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development Our immune system, according to this study, may not be the only thing playing a role in the development of our MS. The same cells that produce the myelin that coats our nerves may also be…

Appropriate control of immune B-cell numbers and activation in the nervous system is key to preventing inflammation in multiple sclerosis (MS), according to a study. These findings also showed that patients with higher levels of a specific B-cell-regulating cell type had less disease activity. The study, “…

How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study I keep a close eye on reports about B-cells and T-cells because they’re the targets of Lemtrada, which is my current disease-modifying therapy. (The DMT Ocrevus targets B-cells alone). So, this…