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‘Biologics’ are protein-based drugs derived from living organisms and are designed to either inhibit or augment a specific component of the immune system. Examples include antibodies directed against very specific molecular components of the immune response, for example, pro-inflammatory cytokines, or naturally occurring cytokine inhibitors such as IL-1 receptor antagonist (IL-1ra).

Elucidation of the cellular and molecular mediators of tissue injury in Crohn’s disease (CD) and ulcerative colitis (UC) has expanded the potential management options for these diseases. The discovery of immunologic and inflammatory mediators, in particular, has paved the way for clinical research with biologic agents in this area. Although conventional treatments remain viable options for some patients, those who are intolerant to these agents and those with more serious or refractory disease may require newer biologic therapies.

Multiple sclerosis (MS) is one of the commonest causes of neurological disability in young adults. Currently more than 1.2million people are affected worldwide by this disease, and the relapsing-remitting form of MS exhibits a gender disequilibrium of 3:1 for female affliction. There are several lines of evidence that multiple sclerosis is an autoimmune disease, which may be modified by genetic factors (see review in Compston et al. 2005 ). Following the initial formulation of the disease concept by the great French neurologist Jean-Martin Charcot in the 1860s, virtually hundreds of (bizarre) remedies were proposed over the subsequent 100 years. The approval in 1993 of interferon- q -1b as the first immunomodulatory treatment for relapsing-type MS represents a milestone in MS therapeutics. In view of the limited efficacy of these agents, the search must continue for better, more effective therapies.

Primary cutaneous lymphomas (PCL) are defined as clonal proliferations of malignant T or B lymphocytes that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. They can be distinguished into cutaneous T-cell lymphomas (CTCL), cutaneous B-cell lymphomas (CBCL) and the rare precursor dendritic cell neoplasms. The PCL are now classified in the new WHO-EORTC classification ( Willemze et al. 2005 ; Table 14.1).

Treatment of cancer should be as potent as possible to completely destroy the tumor. However, precisely this aggressiveness often causes severe side effects. Indeed, due to the side effects, some promising therapeutics cannot be applied systemically. In addition, therapeutics like cytokines which physiologically function in a para- or autocrine fashion require a locally enhanced level to exert their effect appropriately. An elegant way to accumulate therapeutic agents in the tumor is by their conjugation/fusion to tumor-specific antibodies. This chapter presents an overview with preclinical and clinical data for different agents which were turned into targeted therapeutics.

Based on his observations from selective histological staining of bacteria, Paul Ehrlich in 1900 published his idea that certain compounds could be used as “magic bullets” to selectively target external pathogens or even tumours ( Ehrlich 1900 ). With the description of the hybridoma technology by Köhler and Milstein in 1975, the production of targeted monoclonal antibodies (mAbs) became possible and Paul Ehrlich’s dream of magic bullets a reality. Currently, more than a dozen mAbs are licensed ( Reichert et al. 2005 ), and more promising products are about to enter clinical development. While the first antibodies were of completely murine origin due to the underlying technology, scientists started an “evolution” of mAbs in order to reduce immunogenicity ( Borchmann et al. 2001 ). Murine proteins are highly immunogenic, and continuous use in humans in most cases is not possible due to the occurrence of neutralizing antibodies, leading to loss of efficacy and/or safety problems like infusion reactions. Therefore, chimaeric antibodies such as infliximab (Remicade) were developed, reducing immunogenicity by replacement of the murine Fc part by the human counterpart.

The availability of the human genome sequence in the last decade has powered a new wave of protein therapeutics. Using a wide variety of bioinformatics technologies, it has been possible to identify a nearly complete list of all secreted proteins including important bio-therapeutic classes of cytokines, growth factors and hormones.

Since the first articles by Sackett in the 1990s ( Sackett and Rosenberg 1995 ), evidence based medicine (EBM) has developed considerably. Defined as “the integration of the best research evidence with clinical expertise and patients’ values”, EBM is an attempt to improve the care of our patients.