Rationale for cytotoxic monoclonal antibodies in MS

Monoclonal antibodies (MAbs) have been used to treat human disease for over 20 years, and have found a range of applications, predominantly in inflammatory and neoplastic disorders. They are attractive therapies due to their unique specificity and capacity for production on an industrial scale. Cytotoxic MAbs, those that trigger lysis of their cellular target, were first used to probe experimental allergic encephalomyelitis, the standard animal model of MS. Since then, antibodies with specificity for a variety of lymphocytic antigens have been used in MS, with variable results. On the basis of experience with the anti-CD52 antibody, alemtuzumab (Campath-1H), it has been postulated that clinical efficacy of some MAbs in MS may not result from cellular depletion, but from the immunomodulatory effect of the subsequent immune system reconstitution.