BioWa antibodies 'the ultimate warriors' to fight cancer
antibody's ability to initiate the complement immune system and
blow holes in tumour cells.
The technology comes from BioWa's parent company Kyowa Hakko Kogyo - Japan's largest biotech - where scientists have taken parts of Immunoglobulin G3 (IgG3) antibody molecules and inserted them into IgG1 molecules, which is the standard isotope used in therapeutic monoclonal antibodies (mAbs). This is in an attempt to increase their complement-dependent cytotoxicity. The technology could lead to a new type of antibody that are effective at lower doses and could therefore be used as a monotherapy. BioWa also said that the new class of drug could have fewer side effects compared to antibodies carrying radioisotopes or toxic payloads. Since IgG3 molecules have an increased ability to bind to receptors and initiate the complement system, compared to IgG1 antibodies, the resultant IgG3/IgG1 chimer is more effective at destroying tumour cells than either type of immunoglobulin alone. The complement system causes the target cell membrane to be punctured, which, in turn, causes cell lysis and death. The new type of antibodies also retain the desirable features of standard IgG1 molecules, such as antibody-dependent cell cytotoxicity (ADCC), good pharmacokinetic profile and Protein A binding, according to BioWa. This new 'Complegent' technology is actually the second piece of technology pioneered by BioWa to improve antibody potency. It will now be bundled with the first piece of technology - called 'Potelligent' in a newly launched AccretaMab platform. BioWa claims the combined technology has "the potential to be the ultimate antibody warriors to annihilate tumour cells." The Potelligent technology concentrates on improving ADCC, where an antibody binds to an antigen on tumour cells and then to Fc receptors on monocytes, macrophages, and natural killer cells, for example. These cells then engulf the tumour cell and destroy it. This is the mechanism at work with Genentech and Biogen Idec's Rituxan (rituximab), which targets the CD20 antigen. However, the scientists at Kyowa Hakko Kogyo realised that removing fucose from sugar chains on an antibody, enhances ADCC through increased affinity to Fc?RIIIa (CD16), the major Fc receptor for ADCC in humans. The technology also reduces the negative effect of genetic polymorphisms on an antibody's effectiveness. The fucose-free antibodies are manufactured using cells where the FUT8 gene has been suppressed. It is this gene that is responsible for adding fucose to sugar chains in antibodies. These cells are exclusively licensed to BioWa. The company has used the Potelligent technology to create several antibodies to treat cancer. However, its most advanced drug candidate is BIW-8405, which targets the interleukin 5 (IL-5) receptor as a treatment for asthma. The anti-inflammatory drug is currently in Phase I clinical trials. BioWa's preclinical drug candidates target a variety of receptors, including Ganglioside GM2 and GD2 for various cancers such as brain and lung, and vascular endothelial growth factor receptor (VEGF-R, FLT-1) to treat breast and colon cancers. So far, several 'big names' have licensed the Potelligent technology, such as Genentech, Biogen Idec, Medarex, MedImmune and Takeda. BioWa will be hoping the Complegent technology proves just as popular.
