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Neurol Sci (2011) 31 (Suppl 3):S283S288 DOI 10.1007/s10072-010-0382-6
OPENING LECTURE
The advent of monoclonal antibodies in the treatment of chronic autoimmune diseases
Valeria Bruno Giuseppe Battaglia
Ferdinando Nicoletti
Published online: 20 July 2010 Springer-Verlag 2010
Abstract Monoclonal antibodies, rst introduced in cancer therapy and to prevent allograft rejection, represent new pharmacological tools for the treatment of autoimmune diseases. With the knowledge of immunological movements in autoimmunity, it is now possible to target each single step of the immune process, from the activation of T lymphocytes in lymph nodes to the formation of the immunological synapse, and to T cell differentiation and cytokine production. However, this approach is still not devoid of adverse effects. In fact, even if monoclonal antibodies exert selective immunomodulation by targeting only cells expressing a specic antigen, a widespread perturbation of the immune system is induced, leading to a predisposition for infections and infestations and to the occurrence of tumours.
Keywords Biological drugs Monoclonal antibodies
Autoimmune diseases Multiple sclerosis
Introduction
Monoclonal antibodies (mAbs) belong, with fusion proteins (obtained by fusing a proteic portion of a cell surface antigen with CH2 and CH3 regions of an IgG), to a new class of drugs, termed biological drugs. mAbs, which are currently used in basic research and in diagnostic
laboratory tests, have been introduced in therapy for the treatment of cancer and today they have revolutionized the treatment of autoimmune diseases. Advances in knowledge of the immunological movements in autoimmune diseases and in bioengineering have led to new therapeutic concepts that allow the targeting with mAbs of almost all aspects of the inammatory/immune process.
The basis of mAb technology was rst reported by Kohler and Milnstein in 1975 [1] and in 1984 they were awarded the Nobel Prize for this seminal work. In 1986 the rst murine mAb directed against the pan-T cell antigen CD3 was licensed for the treatment of allograft rejection, but due to the high incidence of allergic reactions for the strong human anti-mouse antibody response, the development of less immunogenic mAbs led to the introduction of antibodies with greater human protein content. Today chimeric (human constant region and murine variable region, sufx xi, 34% murine), humanized (human antibody with murine complementarity-determining regionCDR, sufx zu,\10% murine) and fully human (sufx u) mAbs...