EBV Immunotherapy Works in MS

Increasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy.

An open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses.

Of the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (P = 0.033, Fisher's exact test).

EBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS.

Hurray, You say. 

However, I say we have to look at the results. It is clearly not a cure, notably in the people with strong responses. 

There are claims that it effects some symptoms. How is it working?

It's open access so you can read it.

Well done to Prof Pender for getting off the ground and there are benefits reported however.

It is suggested that there is an effect on fatigue. This could be due to an anti-inflammatory effect, but it is not that compelling.

The median Fatigue Severity Scale score  for the combined group of 10 treated patients was lower at week 27 than at week 1 (P = 0.0547). 

Yes this means there was NO difference the null hypothesis that there is no difference is accepted.. 

CSF IgG analysis was performed before and after T cell therapy in 9 patients. The CSF IgG index and intrathecal IgG synthesis had decreased at week 27 compared with baseline in 4 of the 9 patients (participants 1, 6, 9, and 13), 3 of whom showed neurological improvement (participants 1, 9, and 13). There was no detectable change in the pattern of CSF oligoclonal IgG bands after T cell therapy. Notably, in participant 9, whom we first treated with EBV-specific T cell therapy in 2013 and treated again in 2017 in this trial, the CSF IgG index and intrathecal IgG synthesis decreased after the first course of treatment in association with clinical improvement, increased 3.5 years after treatment in association with worsening symptoms, and again decreased after retreatment, in association with clinical improvement.

We have to remember this is a safety study and this shows that the treatment is safe. The people in the trial had progression and we know that this is not the best population to show immunomodulatory effects. 

Anyway the approach is not dead and we will see more on this approach. Have a read and see what you think.

If the Glass Half Full ProfG did this you may have a more positive spin. A company is now taking the lead. However, I fear that they are making a mistake not using autologous cells (i.e from the person who is going to recieve the cells) , but allogeneic made from someone else. Immunology theory thrown out of the window, even if there is a major HLA match, there will be significant mismatch.