Wednesday, 26 June 2013

Alemtuzumab in mice

Turner MJ, Lamorte MJ, Chretien N, Havari E, Roberts BL, Kaplan JM, Siders WM.Immune status following alemtuzumab treatment in human CD52 transgenic mice. J Neuroimmunol. 2013 Jun 4. doi:pii: S0165-5728(13)00115-X. 10.1016/j.jneuroim.2013.04.018. [Epub ahead of print]
Alemtuzumab is a monoclonal antibody against the CD52 antigen present at high levels on the surface of lymphocytes. While treatment of multiple sclerosis patients with alemtuzumab results in marked depletion of lymphocytes from the circulation, it has not been associated with a high incidence of serious infections. In a human CD52 transgenic mouse, alemtuzumab treatment showed minimal impact on the number and function of innate immune cells. A transient decrease in primary adaptive immune responses was observed post-alemtuzumab but there was little effect on memory responses. These results potentially help explain the level of immunocompetence observed in alemtuzumab-treated MS patients.

This study looks at the effect of lemtrada in mice, which have the target. In mice it has not much effect on the innate system and it had a transient effect on the immune arm and no much effect on memory cells. This just shows us the difference between mice and man. You give alemtuzumab to people and their T cells are gone for a few years but in mice they cells are replaced within a few weeks.

However not keeping your subject under constant immunosuppressing conditions will of course allow immune cells to expand and get rid of infections. Rather than tell us what happens in mice it is easier to see how the body responds to infection after vaccination

4 comments:

  1. Surely a mouse's life expectancy is only a couple of years, therefore, a few weeks in micelife equates to a few years in humans?
    Has there been a study on vaccination post-alemtuzumab?

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    1. That's true but a good model (such as ours) can recapitulate many of the hallmarks of MS such as relapses, remissions, secondary progression and development of associated problems such as limb spasticity. Granted, this is accelerated but given that some of our studies can take 6 months or more, that is a good thing!
      Not aware of any studies looking a vaccination efficacy after alemtuzumab.

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    2. There has been a study, but the results are only published in abstract form (i.e. not as a full paper, I presume they are waiting for greater numbers). They looked at Pneumovax II (pneumococcal vaccine), Revaxis (tetanus, diphtheria and inactivated polio viruses 1, 2 and 3) and Menitorix (Haemophilus influenzae type b and Neisseria meningitidis group C), all of which are pretty standard vaccinations in the UK (usually given in childhood). VAccines were given at l;east 3 months post-alemtuzumab.
      Patients had protective levels of antibodies to tetanus and diphtheria prior to re-vaccination; 11/13 patients had a response to Mentorix (compared to 100% controls). The authors conclude that vaccination response is not lost post-alemtuzumab treatment and immunity remains if you have been vaccinated previously.
      However the numbers are small, and so it is difficult to draw wide ranging conclusions.
      The full abstract is here http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=138008&XNSPRACHE_ID=2&XNKONGRESS_ID=150&XNMASKEN_ID=900
      and i think you can view the poster here http://www.posters2view.com/ECTRIMS2011/data/694.pdf
      for those that are interested!

      ruth

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  2. Dr Ruth is correct. I can add that our paper on vaccination after alemtuzumab is accepted to be published in the journal Neurology. Not sure when. Alasdair Coles

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