Simultaneous targeting of VEGF-A and PlGF by VEGF-Grab potentiates the anti-tumor effect of radiation therapy

Abstract

Clinical trials in recent years have tested the combined anti-tumor effects of radiotherapy and anti-VEGF-A therapy, but its clinical benefit of increased overall survival has been proven to be insufficient. In this study, I rationalized and investigated the benefit of combining VEGF-Grab, an anti-angiogenic drug that inhibits VEGF-A and PlGF, with radiotherapy for anti-cancer therapy. By in vitro and human sample analyses, I showed that PlGF is increased in response to radiotherapy. Then, using a syngeneic mouse tumor model, I demonstrated the most potent anti-tumor effects of combined VEGF-Grab and radiation treatment, which was achieved partially by tumor vessel normalization and polarization of tumor-associated macrophages to anti-tumorigenic M1-type. Finally, I showed that VEGF-Grab is not only efficacious but also more effective than a previous developed anti-angiogenic drug, VEGF-Trap, in human xenograft model. In conclusion, this study suggests VEGF-Grab as a viable therapeutic option in the context of inhibiting secondarily activated pathways, specifically in combination with radiotherapy.