![]() ![]() Second, antibodies could kill tumor cell through the activation of human immune system. For example, Cetuximab is an anti-EGFR (Epidermal growth factor receptor) antibody while Bevacizumab binds to EVGF (vascular endothelial growth factor) and inhibit its interaction with VEGF receptor. First, antibodies can bind to signaling molecules mainly growth factor receptors or their ligands, thus blocking the activation of signaling pathways important to the proliferation and survival of tumor cells. There are several mechanisms for monoclonal antibodies to treat cancers. Ĭolorectal cancer Non-small cell lung cancer (NSCLC) Breast cancer Kidney cancer GlioblastomaĢ004 (United States) 2006 (United States) 2007 (European) 2007 (European) 2009 (United States) However, it seems that immunogenicity is so complicated that even fully humanized antibodies like Vectibix and Humira, two antibodies recently launched for targeted therapy, were found to be highly immunogenic. Recently, the development of phage display and transgenic mice technology made it is possible to produce fully humanized antibodies for clinical applications. Despite low incidence, chimeric and humanized monoclonal antibodies still have the potential to stimulate the production of HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody). Chimeric antibodies consists of variable regions from murine antibody and constant regions from human antibody while humanized antibodies were basically human origin except that complementarity-determining regions (CDRs) were derived from the mouse. Since the late 1980s, several humanization strategies such as chimeric antibodies and humanized antibodies have been applied to reduce HAMA-mediated responses. In early 1980s, most of monoclonal antibodies were completely murine that could invoke an immune response resulting in their rapid removal from the blood and systemic inflammatory effects through the production of human anti-mouse antibodies (HAMA) when administrated in humans. Throughout the development of monoclonal antibody, there have been four major types: murine, chimeric, humanized and fully human. ![]() In the other hand, antibodies conjugated with toxins, radioactive particles, drug-activating enzymes, or liposomes carrying che-motherapeutic drugs could restrain the toxicity specifically to cancer cells and reduce systemic side effects, thus improving the efficacy of targeted therapy. Naked antibodies alone could initiate multiple immunological responses to eliminate cancer cells. Antibodies were used clinically in naked or conjugated form. After the development of hybridoma technology by Köhler and Milstein in 1970s, monoclonal antibodies were becoming the major choice of targeted therapy for cancers.
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