Sunday, 13 November 2011

Research: T cell vaccination don't look good.

Fox et al. A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. Mult Scler J. 2011 [Epub ahead of print]

Background: Tovaxin is an designer T-cell immunotherapy (tailored to each individual) under investigation for the treatment of MS. The product consists of in vitro expanded (grown in cell culture), myelin-reactive T-cells manufactured to react with up to six parts of three different myelin proteins. The production renders the cells unable to grow but is geared to make the body produce regulatory cells that control T cells reacting to the myelin proteins

Fig: T cell (purple) interacting with an antigen presenting cell; T cell vaccines are meant to change how these T cells get activated.
Methods: A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing-remitting MS and clinically isolated syndrome subjects.

Results: Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease-modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naïve subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR≥1, ARR>1). However, clinical benefit was not was accompanied by a treatment-dependent improvement in MRI measures.

Conclusions: Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment-naïve individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration.

"Phase II trials are geared to detect whether a treatment is safe rather than to show a treatment effect, which is the aim of the phase III study. However, rather than conclude that people who have previously been treated do not do relapse as much as those who have not been treated, I would suggest that the study provides no evidence that the drug works!

CoI:None

5 comments:

  1. Could you say something about why you think this approach wont work

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  2. Maybe good to call me on this on this one. I did not say it will not work....because I don't know one way of another.

    The basis of this apporach is to to take myelin reactive T cells and x-irradiate them and then inject them back to trigger regulatory cells. This has been done in a number of clinical trials over the past decade or more. Some with claims of some level of activity at inhibtion of relapse.

    This works by creating regulatory cell response to the antigen reactive receptor on the T cell. This is called an idiotype response. There are many scientists that think this type of anti-response creates a network that can be regulatrory of immune responses, I think that it may be too complex and an not sure sure why you need to evoke such a complex mechanism to quell established immune responses.

    My own experience of trying to do this experimentally has met with failure, hence perhaps my blinkered view. I should have kept these comments to myself.

    I have no experience with Tovaxin.

    This approach is developed by Opexa and they have recently been fast tracked for testing in progressive MS (NOV 2011). Here I have concerns because immunoregulatory approaches have consistently failed in progresive MS.

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  3. No reason for you to keep comments to yourself. I asked out of curiosity.

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  4. Dear Anon 7:27.

    Your response was spammed by google I don't know why or how.

    The reason I should probably keep comments to my self is that these are things in development and I have no desire to slate something that I have not experience of, if it gives influence on whether to go on future trials.

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  5. Hello,

    You have provided a very good site to knowing about T-cells. These are a sub group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system...

    ReplyDelete

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