Conventional antibodies: requirements and methods for their optimization

Eighteen years after the discovery of monoclonal antibodies (MAbs), the debate as to whether these reagents have fulfilled their promise must now be addressed. When MAbs were studied as tools for diagnosis and therapy, problems arose regarding the reagents themselves and the recognized target antigens. Because most MAbs are of murine origin, they usually evoke an immune response in human patients, which reduces their effectiveness. Moreover, their bulky size and dispersal via the blood prevent most of the injected antibodies from substantially penetrating solid, poorly vascularized tumors. However, MAbs that are adequately selected and manipulated to circumvent these problems have been found to successfully image tumors and to be therapeutically active.