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 of Clinical Investigation Insightin a study titled “Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.”
ATA190 is a T-cell immunotherapy that targets immune B-cells and plasma cells in the brain and spinal cord that have been infected with EBV. There is increasing evidence linking EBV infection with MS.
ATA190 is made from a patient’s own (autologous) immune cells, which are collected and modified in a lab to target the EBV-infected cells, then infused back into the patient’s blood. The goal is for the modified immune T-cells to recognize EBV-infected B-cells and kill them.
The Phase 1 trial (ACTRN12615000422527), conducted at the QIMR Berghofer Medical Research Institute and The University of Queensland, in Australia, evaluated the safety and efficacy of ATA190 as a treatment for progressive MS.
The study enrolled 10 patients — five with primary progressive MS (PPMS) and five with secondary progressive MS (SPMS). Patients had experienced progressive neurological deterioration due to MS for a mean of 10.1 years.
Participants were treated with four escalating doses of ATA190, administered intravenously over a period of eight weeks. The lowest and first dose was 5 million modified T-cells, followed by doses of 10, 15, and 20 million. Patients were followed for 27 weeks after the first infusion.
Results showed that ATA190 was well-tolerated, with no severe adverse events detected during the study. One patient experienced a potential treatment-related adverse event — dysgeusia, a distortion of the sense of taste.
Efficacy was measured by several parameters, including changes in the Expanded Disability Status Scale (EDSS) score, fatigue, as well as cognitive and other neurological parameters. Researchers also analyzed patients’ brains by magnetic resonance imaging (MRI) and tested their cerebrospinal fluid (CSF) — the liquid around the brain and spinal cord — for the presence of antibodies.
Seven of the 10 patients had improvements in neurological parameters — such as increased productivity, cognition, and word finding — accompanied by a reduction in symptoms. These benefits began two to 14 weeks after the first infusion.
Fatigue, one of the most disabling and hard-to-manage symptoms of MS, was reduced across the group — the median Fatigue Severity Scale score was lower at week 27 compared to the beginning of the study. This decrease, however, didn’t reach statistical significance.
Analysis of the CSF showed that levels of antibodies were reduced at the end of the study in four out of nine patients. Moreover, three of those four patients showed neurological improvements.
Patients received T-cells with different degrees of reactivity against EBV. Six patients who received T-cells with strong EBV reactivity showed clinical improvement; three of those experienced improvements in the EDSS score.
The other four patients received T-cells with weak EBV reactivity; of these, one showed improvement. None experienced a change in the EDSS score.
The team said that overall, the results show that the benefits seen are linked with T-cell effects.
“We previously presented promising initial ATA190 results in patients with progressive MS, and [now] the published results confirm our earlier observations,” Professors Michael Pender, of The University of Queensland, and Rajiv Khanna, coordinator of QIMR Berghofer Centre for Immunotherapy and Vaccine Development, the study’s lead authors, said in a press release.
“Findings from the study support growing evidence that targeting EBV-positive B-cells is a potential novel treatment modality for MS and merit additional investigation,” Pender and Khanna said.
“T-cell therapy targeting only EBV-infected B-cells is a treatment modality that could offer favorable safety and durable efficacy,” they wrote, adding that their work “sets the stage for further clinical trials with autologous and allogeneic EBV-targeted T-cell therapy in MS.”
Atara is developing another therapy, ATA188, to eliminate EBV-infected B-cells in the central nervous system. ATA188 uses immune cells from donors, not from the patients themselves — an allogenic therapy.
“We are also advancing an ongoing Phase 1 off-the-shelf, allogeneic ATA188 study in patients with progressive MS across clinical sites in the U.S. and Australia. We look forward to continued development of both programs, including our plans to initiate a randomized ATA190 MS study,” said Dietmar Berger, MD, PhD, global head of research and development of Atara Biotherapeutics.
I can’t help but think this therapy could help many Lyme/MSIDS patients. EBV is often a player in our illness and many have written about it:
https://madisonarealymesupportgroup.com/2017/11/04/24514/ (EBV – A Key Player in Chronic Illness)
Folks with Lyme/MSIDS have been misdiagnosed with EBV: https://madisonarealymesupportgroup.com/2017/04/11/diagnosed-with-ebv-had-lyme/ and others have it as well as tick-borne infections.
The involvement with numerous viruses is quite common in patients as well. https://madisonarealymesupportgroup.com/2018/10/30/study-shows-lyme-msids-patients-infected-with-many-pathogens-and-explains-why-we-are-so-sick/ For the first time, Garg et al. show a 85% probability for multiple infections including not only tick-borne pathogens but also opportunistic microbes such as EBV and other viruses.
“Once microbes start becoming active, inflammation increases and immune functions are further compromised, establishing what I call Chronic Immune Dysfunction (CID). In its weakened state, the immune system allows reactivation of viruses such as Epstein Barr virus (EBV), Cytomegalovirus (CMV), and other similar viruses — all of which most people harbor in their tissues. These viruses are commonly associated with neuroinflammation, and they tend to complicate the picture of LNB.”
This study shows elevated B-cells in those with untreated Lyme: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01634/full
http://simmaronresearch.com/2018/09/post-treatment-lyme-disease-unmasked-immune-holes/ Mouse studies have shown that the Borrelia burgdorferi bacteria that cause Lyme disease hammer the B-cells….
We herein identify plasmablasts as a key B cell population that correlates with resolution of Bb infection and Lyme disease in humans. The authors
They found that B-cells called plasmablasts were elevated prior to antibiotic treatment in patients who returned to health. Plasmablasts are activated B-cells which circulate for a time in the blood in response to an infection. The higher level of plasmablasts in the recovered patients suggests that these patients simply mounted a stronger immune response to the infection. That was kind of a no-brainer, but the strength of the study was that they were able to specify what part of our amazingly complex immune system the problem was in.
They also determined that the patients who returned to health also exhibited significantly greater clonal expansion: their activated B-cells produced more clones designed to target and get rid of the bacteria. Again, in retrospect, not a surprising finding, but one that does open up a possible treatment option that hasn’t previously been available.