The trial results indicate that EBV-specific adoptive T cell therapy is well tolerated and further back this approach in efficacy trials.
Michael Pender, MD, PhD
Atara Biotherapeutics’ recently announced that its investigational autologous Epstein-Barr virus (EBV)-specific T-cell immunotherapy ATA190 demonstrated positive results in phase 1 testing for patients with progressive multiple sclerosis (MS).
An open-label phase 1 trial (ACTRN12615000422527) was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of ATA190 and evaluate its safety and efficacy as treatment.1 Study participants experienced progressive neurological deterioration due to MS for a mean of 10.1 years.
“We previously presented promising initial ATA190 results in patients with progressive MS, and the published results confirm our earlier observations,” Michael Pender, MD, PhD, University of Queensland, and Rajiv Khanna AO, PhD, Coordinator of Queensland Institute of Medical Research Berghofer Centre for Immunotherapy and Vaccine Development, said in a statement.2 “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.”
Patients donated a 200-400ml blood sample that was used to generate LMP/EBNA1-specific T-cells for 2—4 adoptive transfers. Once the cells passed quality assurance assessment, treatments were scheduled. The 4 escalating doses of ATA190 were administered intravenously over a period of 8 weeks; the lowest and first dose was 5 million modified T-cells, followed by doses of 10, 15, and 20 million. Study participants received T-cells with various degrees of reactivity against EBV. Safety and efficacy were monitored for 27 weeks and included Expanded Disability Status Scale (EDSS) score, fatigue, cognitive and additional neurological assessments, as well as analyses of magnetic resonance imaging and cerebrospinal fluid immunoglobin G (IgG) production.
Primary outcomes included determining if autologous LMP/EBNA1-specific T-cells can be generated to clinical scale from the blood of patients with progressive MS; the safety of adoptive transfer of LMP/EBNA1-specific T-cells into patients with progressive MS; and the tolerability of adoptive transfer of LMP/EBNA1-specific T-cells into patients with progressive MS.
Researchers reported that symptomatic and objective neurological improvement was seen in 7 of the 10 patients, with the greatest benefit seen in patients that received T cells with strong EBV reactivity. The benefits began 2­—14 weeks after the first infusion. Reduction in fatigue was a consistent and prominent feature in patients showing neurological improvement.
ATA190 was well-tolerated and no severe adverse effects were reported during the study, however, 1 patient experienced a potential treatment-related adverse effect—dysgeusia.
Analysis of the cerebrospinal fluid showed that levels of antibodies were reduced at the end of 27 weeks in 4 out of 9 patients and 3 of the 4 patients showed neurological improvements.
Six study subjects who received T-cells with strong EBV reactivity were reported to show clinical improvement and 3 of those experienced improvements in EDSS score. Of the participants who received T-cells with weak EBV reactivity, only 1 showed improvement; and no change in EDSS score was observed.
A randomized autologous phase 2 trial is planned for several locations in Australia and the United States.
1. Pender M, Csurhes P, Smith C, et al. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight. 2018;3(22):e124714. doi: 10.1172/jci.insight.124714.
2. Atara Biotherapeutics Announces Publication of Phase 1 Study Demonstrating Clinical Improvement in Progressive Multiple Sclerosis Patients Treated with ATA190, An Autologous Epstein-Barr Virus (EBV)-Specific T-Cell Immunotherapy [news release]. South San Francisco, Calif.,: Atara Biotherapeutics; Nov. 19, 2018. http://investors.atarabio.com/news-releases/news-release-details/atara-biotherapeutics-announces-publication-phase-1-study. Accessed Dec. 11, 2018.