IGG Levels in Comparison With WBC and Immune Response

Abstract

Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. The modulation of angiogenesis pathways using small interfering RNA (siRNA) inhibitors of gene expression has proven to be a powerful approach which would be applied for treatment of multiple cancers. Using a nanoparticle-mediated systemic delivery of siRNA with a dual targeting specificity to both neovasculature and VEGF receptor 2 (KDR), we were able to achieve anti-tumor efficacies in multiple tumor models. We further tested this potential anticancer drug candidate, ICS-283, in combination with Genentech's Avastin, a mAb against VEGF A in colorectal tumor cell DLD-1 xenograft model. The combined regimen resulted stronger anticancer efficacy than either of the component alone with significant evidence of anti-angiogenesis activities. We will report the latest results of this novel approach, further discuss the underlined mechanism action of this mAb-siRNA combination for potent anti-angiogenesis therapy and its clinical implication for cancer treatment. The dual-targeted therapeutics and the combination of siRNAs targeting multiple pro-angiogenesis factors have further demonstrated the advantages of this novel therapeutic modality. As with any emerging technologies, many issues related to siRNA therapeutics must be addressed diligently before the success of this novel approach can be achieved in clinics.