Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic

Author(s): Feng Gao*, Chun Yang

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 1 , 2020

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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.

Keywords: Cancer immunotherapy, immune checkpoint inhibitors, combination cancer therapy, PD-1/PD-L1 mechanism, tumor angiogenesis, VEGF/VEGFR2 signaling.

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VOLUME: 20
ISSUE: 1
Year: 2020
Page: [3 - 18]
Pages: 16
DOI: 10.2174/1568009619666191114110359
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