Many chronic inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, and Crohn's disease to name just a few are caused by an overreactive immune system. Carrier substances that falsely inform the body about an ongoing infection are produced in large quantities. The immune system answers by starting a strong immune response. The body's own tissues are attacked and continuously destroyed. Specific models of reaction have to be understood to find a possible key to altering this perpetual process of destruction. On the other hand, the immune system may overlook the destructive process of cancer by neglecting its surveillance task, by allowing itself to be fooled by the tumor cell's deceiving tactics. Here specific biologic reagents are needed to jump-start the immune reaction or simply for highly specific targeting of drugs to kill specifically the tumor. The development of biologics has both of these aims in mind.
By definition biologics are proteins and/or derivatives thereof that modulate the immune system, down-regulate the inflammatory response or support tumor specific defenses. Biologics - also known as "biologi-cals" or "recombinant therapeutics" - do not represent one homogeneous group of drugs. Monoclonal antibodies, fusion proteins (along with other proteins, toxins and radionucleotides) and recombinant proteins, growth factors, anti- and pro-angiogenic factors, and expression vectors generating proteins in situ may all be included as members of this class of pharmaceuticals.
These drugs are designed to resemble or exploit substances that occur naturally in the body and are thereby able to influence the immune response. Advances in biotechnology and molecular biology have made their production possible and further advances are necessary to widen their field of use.
Part I of the book describes the process of development of biologics, starting with the rationales of the research labs of public institutions and also of the pharmaceutical industry. As we have limited our focus to drugs having reached clinical use, the pre-clinical part is also biased towards the success stories: It starts by defining this class of medications, which are not always recognizable as a group. The development and pre-clinical pharmacology of biologics are exemplified by looking at infliximab, adalimumab, etanercept and efa-lizumab. Part I also provides introductions to monoclonal antibody targeted radiation cancer therapy and the details of the production process, safety precautions and - last but not least - the profit margins necessary for the manufacture of biopharmaceuticals.
In order to understand the background and possible problems with biologics at a more detailed level, the pre-clinical descriptions in Part I are followed by details of their clinical use in Part II. This part describes clinical studies and practical experience by presenting disease-specific applications and clinical trials. Biolog-ics today have a broad use in medicine mainly in a group of diseases referred to as "immune-mediated inflammatory diseases" (IMIDs), comprising psoriasis and psoriatic arthritis, rheumatoid arthritis, colitis and multiple sclerosis, but also in the treatment of tumors of the skin and other organ systems. Moreover, they continue to find their way into other medical fields. Biologic therapies for rheumatoid arthritis targeting TNF-a and IL-1 are extensively covered, and the treatments of psoriasis and psoriatic arthritis are also examined in detail. Close attention is then given to the use of biologics such as anti-TNF and the new anti-IL-12p40 antibody in gastroenterology. A growing and promising use of biologics is coming up in neurology, especially for the treatment of multiple sclerosis. Finally, more and more biologics are being successfully applied in the fight against cancer. In some types of cancer, biologics already have a solid basis as treatment, and other types of cancer are still being evaluated to identify the most suitable molecular target to start biologic therapy.
Part III of this book highlights safety aspects and future perspectives, attempting to look into the future by defining possible new targets for biologic therapy. New biological therapeutic strategies in the genome age are discussed and suggested improvements for the safety of biologics are outlined. As biologics are proteins they are theoretically able to activate the immune system themselves and might cause adverse reactions such as antibody formation, which in turn may lead to allergies or neutralization of the drug. Finally, we provide a distillation of the evidence from the point of view of evidence based medicine.
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