Abstract
Angiogenesis-targeted therapy of cancer is considered a promising strategy for therapeutic management of cancer progression. Over the last two decades, a few anti-angiogenesis monoclonal antibodies (mAbs) blocking VEGF signaling have been developed and approved by the FDA. The most widely used anti-angiogenesis drug is bevacizumab which binds VEGFA and prevents its interaction with VEGF receptor leading to suppression of angiogenesis. Despite the remarkable success in development of angiogenesis inhibitory mAbs, their clinical application is limited by the high-cost of mAbs-based regimen which includes multiple doses of mAbs due to their short biological half-life. Antibody gene therapy is an alternative system of antibody production. In this study, we have developed a gene-based anti-VEGF mAb system which is expected to produce a high concentration of anti-VEGFA mAb upon a single administration in cancer patients. The full-length cDNA bevacizumab light and heavy chains joint with T2A sequence were cloned in pCDH lentivirus vector. The lentiviral particles expressing bevacizumab was produced in HEK-293T cells. Recombinant lentiviral particles containing bevacizumab (rLV-bev) efficiently transduced HEK-293cells and produced functional bevacizumab mAb. Bevacizumab expression in the transduced cell was assessed by qRT-PCR and western blot at both the mRNA and protein level, respectively. The functionality of the recombinant bevacizumab was confirmed using the tube formation assay in the co-culture system of endothelial cells and HT-29cells transduced with rLV-bev viral particles. Our results show that rLV-bev gene therapy can be useful for angiogenesis-targeted therapy of cancer.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.