Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis

Department of Neurology, University Hospital of Wales, Heath Park, Cardiff, UK.
Journal of Neurology (Impact Factor: 3.38). 02/2008; 255(2):231-8. DOI: 10.1007/s00415-008-0696-y
Source: PubMed


Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years. The mean annualised relapse rate fell from 2.48 pre treatment to 0.19 post treatment with 29% of documented relapses observed in the 12 weeks following initial infusion. Mean change in EDSS was -0.36 overall and -0.15 in those patients completing > or =1 year of follow- up. Eighty-three per cent of patients had stable or improved disability following treatment. Infusion related side effects were common including rash, headache and pyrexia but were usually mild and self limiting. Transient worsening of pre-existing neurological deficits during infusion was observed in 3 patients. 12 patients developed biochemical evidence of autoimmune dysfunction, 2 patients developed thyroid disease and 1 patient autoimmune skin disease. We conclude that relapse rates fall following Campath 1-H. Whilst side effects were common these were normally self limiting or easily managed, suggesting Campath 1-H may be of use in the treatment of very active relapsing remitting multiple sclerosis.

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Available from: Adrian A Pace, Feb 21, 2015
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    • "CD8 + cells appear at high frequencies within CNS lesions (Babbe et al., 2000) and parenchyma and are also enriched within the CSF of patients with relapsing–remitting MS (Jilek et al., 2007; Malmestrom et al., 2008). Although depleting all lymphocytes with the anti-CD52 mAb Campath 1-H can reduce clinical signs in patients with relapsing–remitting and secondary progressive stages of MS (Coles et al., 2006; Hirst et al., 2008), trials that selectively targeted only CD4 + T cells showed limited benefit (Racadot et al., 1993; Rumbach et al., 1996; van Oosten et al., 1997), suggesting that CD8 + T cells might also be an important target. Others have suggested that transfer of myelin oligodendrocyte glycoprotein (MOG)reactive CD8 + T cells can also induce EAE (Sun et al., 2003; Ford and Evavold, 2005). "
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    ABSTRACT: CD4⁺ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8⁺ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4⁺ versus CD8⁺ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type (WT) C57BL/6 mice. We show that MOG(-/-) mice have enhanced sensitivity to immunization with the immunodominant peptide of MOG (35-55), as evidenced by increased expansion of both CD4⁺ and CD8⁺ T cell subsets. Most strikingly, CD8⁺ T cells from MOG(-/-) mice responded to a novel T cell epitope which binds to MHC class I with high affinity. Despite this, MOG-responsive CD8⁺ T cells sourced from either WT or MOG(-/-) mice failed to initiate CNS inflammation upon transfer to MOG-sufficient mice. In our hands, this capacity was only found in CD4⁺ T cells. However, MOG(-/-) CD4⁺ cells did not show greater pathogenic activity than their WT counterparts. Our data indicate that, in the presence of endogenous MOG, CD8⁺ T cells capable of responding to a MHC class I-restricted epitope that can be stably expressed are subject to rigorous control through central and/or peripheral tolerance.
    Frontiers in Immunology 05/2011; 2:17. DOI:10.3389/fimmu.2011.00017
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