Author Interviews, Immunotherapy, Multiple Sclerosis / 27.11.2018
Multiple Sclerosis: T Cell Immunotherapy Targeting EBV Infected Cells Shows Promise
MedicalResearch.com Interview with:
[caption id="attachment_46225" align="alignleft" width="142"]
Dr. Berger[/caption]
Dietmar P. Berger, MD, PhD
Head of Global R&D
Atara Biotherapeutic
MedicalResearch.com: What is the background for this study?
Response: Epstein-Barr virus (EBV) is present in B lymphocytes, plasma cells and epithelial cells of over 95% of individuals over the age of 40. Multiple studies have shown that nearly all patients with Multiple Sclerosis (MS) are EBV positive, including a recent presentation at the 2018 ECTRIMS Congress in Berlin that showed 100% of MS patients are positive for EBV (Ruprecht et. al). Current B cell directed therapies such as anti-CD20 therapies have demonstrated an effect on Multiple Sclerosis activity. These therapies work by depleting B cells including those infected by EBV.
Our belief is that loss of EBV-specific T cell function (e.g., T cell exhaustion) occurs in patients who develop Multiple Sclerosis, which results in the accumulation of EBV infected B and plasma cells in the CNS leading to the autoreactive immune cycle seen in MS patients. The increasing evidence of a link between EBV infection and the development of MS led to the initiation of a Phase 1 study to investigate the use of an autologous T-cell immunotherapy (ATA190) to selectively target and deplete EBV infected cells in patients with progressive MS.
As T cell immunotherapies (like ATA190) are designed to penetrate the central nervous system, this approach was felt to be particularly useful in Multiple Sclerosis where the inflammatory response and infected B lymphocytes and plasma cells are inaccessible inside the CNS to the vast majority of classic targeted agents.
Dr. Berger[/caption]
Dietmar P. Berger, MD, PhD
Head of Global R&D
Atara Biotherapeutic
MedicalResearch.com: What is the background for this study?
Response: Epstein-Barr virus (EBV) is present in B lymphocytes, plasma cells and epithelial cells of over 95% of individuals over the age of 40. Multiple studies have shown that nearly all patients with Multiple Sclerosis (MS) are EBV positive, including a recent presentation at the 2018 ECTRIMS Congress in Berlin that showed 100% of MS patients are positive for EBV (Ruprecht et. al). Current B cell directed therapies such as anti-CD20 therapies have demonstrated an effect on Multiple Sclerosis activity. These therapies work by depleting B cells including those infected by EBV.
Our belief is that loss of EBV-specific T cell function (e.g., T cell exhaustion) occurs in patients who develop Multiple Sclerosis, which results in the accumulation of EBV infected B and plasma cells in the CNS leading to the autoreactive immune cycle seen in MS patients. The increasing evidence of a link between EBV infection and the development of MS led to the initiation of a Phase 1 study to investigate the use of an autologous T-cell immunotherapy (ATA190) to selectively target and deplete EBV infected cells in patients with progressive MS.
As T cell immunotherapies (like ATA190) are designed to penetrate the central nervous system, this approach was felt to be particularly useful in Multiple Sclerosis where the inflammatory response and infected B lymphocytes and plasma cells are inaccessible inside the CNS to the vast majority of classic targeted agents.
Dr. Mangione[/caption]
Dr. Carol Mangione M.D., M.S.P.H., F.A.C.P
Ronald Reagan UCLA Medical Center
Division Chief of General Internal Medicine and Health Services Research
Professor of Medicine.
Barbara A. Levey, MD, and Gerald S. Levey, MD
Endowed chair in medicine David Geffen School of Medicine
University of California
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Unhealthy alcohol use is relatively common and is increasing among U.S. adults. Alcohol use is the third leading cause of preventable death in the U.S. and contributes to more than 88,000 deaths per year. In pregnancy, it also leads to birth defects and developmental problems in children. The Task Force found that screening tests and brief counseling interventions can help detect and reduce unhealthy alcohol use among adults, and in turn help prevent negative consequences related to alcohol use. For adolescents ages 12 to 17, clinicians should use their best judgment when deciding whether or not to screen and refer their patients to counseling, until we have better studies available.