A treatment to target EBV has been shown to improve symptoms in some people with progressive MS in a world-first clinical trial.
The small phase I safety trial used an ‘adoptive T cell immunotherapy’ treatment. This involves taking blood from patients, extracting their immune cells, and then ‘training’ these cells in the lab to recognise and destroy EBV. The cells are then reintroduced to the patient’s body and go to work in targeting the EBV hiding in the body.
The trial was carried out by Professor Michael Pender and Professor Rajiv Khanna and MS Research Australia is proud to have contributed to the funding of this project, as well as significantly supporting Professor Pender’s EBV research over the last decade.
What is EBV and its relationship with MS?
EBV is a virus which infects a subset of white blood cells in the body called B cells. Most people won’t know they have had it as it is a common childhood illness with non-specific symptoms, although in adolescents it can cause the more serious glandular fever (infectious mononucleosis).
Once a person becomes infected with EBV, they carry the virus in their B cells for the rest of their life, mostly without any symptoms or problems. The infected cells are usually kept under control by other cells of the immune system called T cells which recognise and kill virus-infected cells.
While we know that EBV is a risk factor for the development of MS, there has been intense research to understand exactly how the virus contributes to MS and how we might tackle it to prevent or treat MS.
How did this EBV trial come about?
Professor Michael Pender, a neurologist and researcher from The University of Queensland and Royal Brisbane and Women’s Hospital has spent much of his career investigating EBV in MS with a great deal of support along the way from MS Research Australia.
Previous studies by Professor Pender’s research group have shown that people with MS have a reduced number of T cells capable of killing EBV-infected B cells, compared with people who do not have MS. This led to the idea that boosting a person’s ability to kill EBV-infected cells might help treat MS.
In recent years Professor Pender has teamed up with Professor Rajiv Khanna from QIMR Berghofer Medical Research Institute to test a novel treatment that targets EBV infected cells in the body.
Professor Khanna had developed a technique where the T cells could be removed from a patient, grown in the laboratory and primed to recognise and destroy EBV infected cells. The T cells are then returned to the patient where they act like heat-seeking missiles to kill the problem cells. He has primarily been testing the type of treatment called ‘adoptive T cell immunotherapy’ on certain cancers that are associated with EBV.
After initially treating just one patient with secondary progressive MS with some success (reported in 2014), the pair set up a phase I clinical trial to test the safety of the therapy in a small group of five people with primary progressive MS and five with secondary progressive MS.
What did the trial involve?
13 people with progressive MS were enrolled into the study. The scientists were able to collect the EBV-targeting T cells from 11 of 13 people and grow them in the laboratory.
One patient had to drop out of the trial before being treated due to an unrelated health condition, leaving 10 patients still in the trial. 5 with primary progressive MS and 5 with secondary progressive MS. The T cells were primed against EBV and then infused back into their body in four doses.
The participants were then monitored for a period of 27 weeks with a range of tests including MRI scans, the EDSS neurological disability scoring system, fatigue, quality of life and thinking and memory skills.
Were there any improvements in MS symptoms?
This very small study was first and foremost designed to identify any safety issues with the treatment, however, it did appear to have some positive effects.
Seven of the 10 participants showed a clinical improvement on the tests of neurological disability. Of the three that did not improve, two remained stable and one experienced worsening of disability.
Overall for the whole group, fatigue was significantly improved across the 27 week period, this being a prominent feature in five of the seven patients who showed neurological improvements.
Thinking and memory skills, while not improved, did not worsen over the period of the study.
In general, the treatment did not appear to prevent the appearance of new or active lesions in the MRI scans of some of the participants, but these people were still among those who did show neurological improvement.
Were there any side-effects?
None of the 10 people experienced any serious side effects as a result of the treatment. Just one patient experienced a minor side effect of an alteration to their sense of taste. This was thought to be due to one of the chemicals used in the preparation of the cells.
What do the results tell us?
The results of the trial firstly show that it is possible to collect and identify the EBV-targeting T cells from the majority of people with progressive MS and grow them in the laboratory.
They also tell us that the treatment appears safe. The findings have been published in the scientific journal JCI Insight. It is a potentially encouraging results for people living with primary and secondary progressive MS. However, it is important to be mindful that this was a very small study that was first and foremost designed to identify any safety issues with the treatment. It is too small, and not designed with the gold-standard placebo controlled, blinded, design to identify whether the treatment was truly effective.
However, the clinical signs of improvement noted in this study are encouraging. In particular, one important observation was that the strength of the EBV-targeting response noted in the preparation of the cells in the laboratory prior to treatment did seem to match with the clinical outcomes. The six participants with a strong reaction to EBV showed clinical improvement, whereas only one of the four participants with a weak reaction to EBV showed clinical improvement of symptoms but not disability.
Professor Khanna is now collaborating with biotechnology company Atara Biotherapeutics to conduct a bigger, randomised controlled (double blind) trial of another ‘off-the-shelf’ version of this treatment – you can learn more about this trial here.
This phase I trial was funded through a grant to Professor Rajiv Khanna and Professor Michael Pender in a partnership between MS Research Australia and MS Queensland and other philanthropic support to QIMR Berghofer Medical Research Institute.