ABSTRACT
The exciting field of therapeutic monoclonal antibodies (mAbs) had its origins as Milstein and Koehler presented their murine hybridoma technology in 1975 (Kohler and Milstein, 1975). This technology provides a reproducible method for producing monoclonal antibodies with unique target selectivity in almost unlimited quantities. In 1984, both scientists received the Nobel Prize for their scientific breakthrough, and their work was viewed as a key milestone in the history of mAbs as therapeutic modalities and their other applications. Although it took some time until the first therapeutic mAb got market authorization from the FDA in 1986 (Orthoclone OKT3, Chapter 17), monoclonal antibodies are now the standard of care in several disease areas. In particular, in the areas of oncology (Chapter 16), transplantation (Chapter 17) and inflammatory diseases (Chapter 18) patients now have novel life-changing treatment alternatives for diseases which had very limited or non-existent medical treatment options before the emergence of mAbs. To date more than twenty mAbs, and mAb derivatives including fusion proteins and mAb fragments are available for different therapies (Table 1): nine mAbs and two immunoconjugates in oncology; six mAbs and three Fc (Fragment crystallization)- fusion proteins in inflammation; three mAbs in transplantation; one mAb fragment for the cardiovascular area). Technological evolutions have subsequently allowed much wider application of mAbs via the ability to generate mouse/human chimeric, humanized and fully human mAbs from the pure murine origin. In particular, the reduction of the xenogenic portion of the mAb structure decreased the immunogenic potential of the murine mAbs thus allowing their wider application. mAbs are generally very safe drugs because of their target selectivity, thus avoiding unnecessary exposure to and consequently
activity in non-target organs. This is particularly apparent in the field of oncology, where mAbs like rituximab, trastuzumab and bevacizumab can offer a more favorable level of efficacy/safety ratios compared to common chemotherapeutic treatment regimens for some hematological and solid tumors.
