ABSTRACT

Therapeutic antibodies have been on a roller coaster ride of expectation and disappointment. In the early days of murine monoclonal antibody (MAb) production, the image and potential of the “magic bullet” appeared very alluring. The harsh realities of bringing this desire to fruition, however, took its toll on many early investigators and commercial companies that fell by the wayside. The increasing availability of new MAbs with therapeutic potential, coupled with the maturation of genetic engineering techniques, has allowed one to consider the treatment of diseases that in the past would have been difficult to envisage. One of the first engineering solutions designed to overcome the problem of human anti-murine antibody, experienced with many murine antibodies, was the construction of chimeric antibodies. Antibody molecules are composed of discrete domains, and each of these major structural protein domains are encoded by separate heavy- or light-chain exons.