A new landmark study from nature provides a long-sought mechanistic link between EBV and multiple sclerosis, extending the findings of a recent scientific paper that identified EBV as the primary cause of multiple sclerosis | Business and finance


Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today welcomed the second high-impact study this month confirming that EBV is the main driver of the development of MS. The article, titled “Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM”, was published today in the journal Nature.

Multiple sclerosis is a chronic neurological disease affecting approximately 2.8 million people worldwide, including approximately 900,000 in the United States. ). Although genetics and environmental factors play a role, it has long been postulated that EBV induces the patient’s immune cells to mistakenly attack myelin.

the Nature adds to the known EBV-MS epidemiological connection by providing a mechanistic basis for how EBV infection can trigger the patient’s immune cells to attack CNS tissues. These results validate molecular mimicry as one of the main mechanisms of EBV-mediated MS, which occurs when fragments of the virus share sequence or structural similarities with certain brain proteins. The immune system can mistake these “self proteins” for EBV. These new data reveal how EBV infection can lead to the development of antibodies that target both EBV and CNS proteins, potentially leading to MS.

Researchers have identified a type of antibody isolated from the cerebrospinal fluid (CSF) of MS patients that strongly binds to an EBV protein, EBNA1, and cross-reacts with the central nervous system protein GlialCAM. GlialCAM is a cell adhesion molecule expressed in a variety of brain cells, including oligodendrocytes which are responsible for myelin production, as well as outside myelin sheaths. This antibody cross-reactivity between EBV and self-proteins was found to result from molecular mimicry due to key similarities between GlialCAM and EBNA1. The group also demonstrated that immunization with EBNA1 in a mouse model of MS exacerbated the disease and generated a strong antibody response against GlialCAM and EBNA1, ameliorating immune cell infiltration and demyelination which are two hallmarks of human MS pathology. MS.

“EBV may be the only risk factor needed to develop MS, given that essentially 100% of people with MS have been infected with EBV. step-by-step of how it causes the immune system to attack a person’s own myelin sheath,” said Lawrence Steinman, MD, professor of neurology and neurosciences, pediatrics and genetics, Stanford University, and study author.”This new research fills these gaps and clarifies how EBV infection can cause MS. New therapies specifically targeting this link are already in development, including ATA188 T-cell immunotherapy.” from Atara, which is actively recruiting for a Phase 2 clinical study.”

the Nature The article complements the findings of a second publication, “Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis”, recently published in the journal Science, and collectively provide new epidemiological and molecular data confirming the role of EBV in initiating and driving the pathophysiology of MS. The cohort study provided compelling epidemiological evidence that EBV infection precedes the onset of MS. The study analyzed 62 million serum samples and followed more than 10 million people in the US military over a 20-year period (1993-2013), showing a 32-fold increase in MS risk after infection at EBV. Of the 801 MS cases identified, 35 were EBV-negative at baseline, with all but one becoming EBV-positive before the onset of their MS, giving a seroconversion rate of 97% compared to 57% in people who have not developed MS. Serum concentrations of neurofilament light chain (sNfL), a sensitive biomarker of nerve fiber damage, increased only after EBV infection, indicating that EBV infection preceded not only the onset of symptoms, but also the timing of the first detectable disease mechanisms underlying MS. Other viral infections, such as CMV, did not increase the risk of MS and were ruled out as contributing factors to the development of MS.

“These studies identify EBV as the primary cause of MS and provide a direct mechanistic link between EBV-induced immune system activation and the autoimmune myelin pathology seen in MS,” said AJ Joshi. , MD, chief medical officer at Atara. “Specifically, these new data further link MS to EBV-infected B cells and plasma cells, highlighting the role of EBV antigens, including the EBNA1 protein, in disease development. Importantly, ATA188, Atara’s investigational MS therapy, targets key epitopes of these antigens, including EBNA1, in hopes of eventually providing a new treatment option for the millions of people living currently with MS. The actively recruiting Phase 2 EMBOLD study, with a formal interim analysis scheduled for the second quarter of this year, will be a major step in this direction.

The full articles are available in digital format and can be viewed via the following links:

About progressive multiple sclerosis

Multiple sclerosis (MS) is a chronic, debilitating, and potentially disabling autoimmune disease of the central nervous system (CNS) that affects myelin, a protein that helps nerves in the brain and spinal cord communicate. There are an estimated 2.8 million people with MS worldwide, of whom around 1.2 million are living with progressive forms of the disease, marked by continuing clinical decline and worsening disability. Although the exact triggers of MS are not fully established, inflammation caused by environmental and genetic factors is suspected. There is growing evidence that EBV, carried by over 90% of the population that infects a particular type of immune cell called a B cell, may play a role in MS and may in fact be the only risk factor identified as necessary to cause MS. With few treatment options available for progressive MS and the ability of these treatments to fundamentally alter disease progression, there remains a critical unmet need.

About Atara Biotherapeutics, Inc.

Atara Biotherapeutics, Inc.(@Atarabio) is a pioneer in T-cell immunotherapy leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases, including solid tumors, hematological cancers and autoimmune diseases. With our flagship program in Phase 3 clinical development and currently under review to support registration in Europe, Atara is the most advanced allogeneic T-cell immunotherapy company and intends to rapidly deliver ready-to-use treatments employment to patients with unmet medical needs. Our platform exploits the unique biology of EBV T cells and has the ability to treat a wide range of EBV-associated diseases, or other serious illnesses through the incorporation of CARs (chimeric antigen receptors) or TCRs (T cell receptors) altered. Atara applies this unique platform, which does not require TCR or HLA gene editing, to create a robust pipeline including: tab-cel in phase 3 development for Epstein virus-induced post-transplant lymphoproliferative disease -Barr (EBV+ PTLD) and other EBV -caused diseases; ATA188, a T-cell immunotherapy targeting EBV antigens as a potential treatment for multiple sclerosis; and multiple next-generation chimeric antigen receptor (CAR-T) T-cell immunotherapies for solid tumors and hematological malignancies. Improving the lives of patients is our mission and we will never stop working to bring transformative therapies to those in need. Atara is headquartered in South San Francisco and our state-of-the-art research, development and manufacturing facilities are based in Thousand Oaks, California. For more company information, please visit atarabio.com and follow us on Twitter and LinkedIn.

Forward-looking statements

This press release contains or may imply “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: the development, timeline, progress and outlook for ATA188 and clinical trials related to ATA188, potential benefits of ATA188, safety profile of ATA188, potential of ATA188 to treat multiple sclerosis multiple sclerosis, the potential market for ATA188, the mechanistic link between EBV and multiple sclerosis, and the ability of ATA188 to specifically target such a link. Because these statements address future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties, and Atara’s actual results, performance or achievements could differ materially from those described or implied. by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, the risks and uncertainties associated with the lengthy and costly pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in southern San Francisco and southern California and on our clinical trial sites, as well as the activities or operations of our third-party manufacturers, contract research organizations or other third parties with whom we do business, (ii) our ability to access capital and (iii) the value of our common stock; the sufficiency of Atara’s liquidity and the need for additional capital; and other risks and uncertainties affecting Atara and its development programs, including those discussed in Atara’s filings with the Securities and Exchange Commission (SEC), including in the “Risk Factors” and “Discussion and Management’s Discussion and Analysis of Financial Condition and Results of Operations” in the latest periodic reports filed by the Company on Forms 10-K and 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

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SOURCE: Atara Biotherapeutics, Inc.

Copyright BusinessWire 2022.

PUBLISHED: 01/24/2022 11:13 AM/DISC: 01/24/2022 11:13 AM

Copyright BusinessWire 2022.

Harry D. Gonzalez