Target therapy of cancer: Implementation of monoclonal antibodies and nanobodies

Abstract

In the past decades, the mainstay of systemic therapy for solid and haematological malignancies was chemotherapy; nevertheless this modality has the drawbacks such as drug resistance and eliciting sever cytotoxicity in the normal tissue. To resolve such downsides, the cancer therapy modalities need to be advanced with more effective and tolerable treatments to specifically target the malignant cell with minimal adverse consequences. In fact, characteristically, the malignant diseases are self sufficiency in growth signals along with insensitivity to growth inhibition. They can also evade from apoptosis, have limitless replicative potential, induce angiogenesis and possess metastasis potential. Given that the most of these characteristics are often due to genetic defects, thus key to the development of targeted therapies is the ability to use such processes to phenotypically distinguish the tumor from its normal counterpart by its specific/selective markers. The therapeutic monoclonal antibodies (mAbs) are deemed to be a class of novel agents that can specifically target and disrupt molecular pathways underlying tumorigenesis. The mAbs are produced by a single clone of B-cells, and are monospecific and homogeneous. Since Kohler and Milstein heralded a new era in antibody research and clinical development by the discovery of hybridoma technology in 1975, more than 20 mAbs have been approved by the US Food and Drug Administration (FDA) for treatment of obdurate diseases, including different types of cancers. Mouse hybridomas were the first reliable source of monoclonal antibodies which were developed for several in vivo therapeutic applications. Accordingly, the recombinant antibodies have been reduced in size, rebuilt into multivalent molecules and fused with different moieties such as radionuclides, toxins and enzymes. The emergence of recombinant technologies, transgenic animals and phage display technology has revolutionized the selection, humanization and production of antibodies. This review focuses on implementation of the mAbs and nanobodies fragments for cancer therapy. © 2009 IOS Press and the authors. All rights reserved.