Title:Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic
Volume: 20
Issue: 1
Author(s): Feng Gao*Chun Yang
Affiliation:
- BuChang (Beijing) Pharmaceutical Co. Ltd, Hongda Industrial Park, Hongda North Road, Beijing 100176,China
Keywords:
Cancer immunotherapy, immune checkpoint inhibitors, combination cancer therapy, PD-1/PD-L1 mechanism, tumor
angiogenesis, VEGF/VEGFR2 signaling.
Abstract: The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling
pathway is one of the most important pathways responsible for tumor angiogenesis. Currently, two
monoclonal antibodies, anti-VEGF-A antibody Bevacizumab and anti-VEGFR2 antibody Ramucizumab,
have been approved for the treatment of solid tumors. At the same time, VEGF/VEGFR2
signaling is involved in the regulation of immune responses. It is reported that the inhibition of this
pathway has the capability to promote vascular normalization, increase the intra-tumor infiltration of
lymphocytes, and decrease the number and function of inhibitory immune cell phenotypes, including
Myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and M2 macrophages. On
this basis, a number of clinical studies have been performed to investigate the therapeutic potential
of VEGF/VEGFR2-targeting antibodies plus programmed cell death protein 1 (PD-1)/ programmed
cell death ligand 1 (PD-L1) inhibitors in various solid tumor types. In this context, VEGF/VEGFR2-
targeting antibodies, Bevacizumab and Ramucizumab are briefly introduced, with a description of
the differences between them, and the clinical studies involved in the combination of Bevacizumab/
Ramucizumab and PD-1/PD-L1 inhibitors are summarized. We hope this review article will
provide some valuable clues for further clinical studies and usages.
