Target intelligence / Profile preview

Programmed cell death protein 1 (PD-1) and Vascular endothelial growth factor A (VEGF-A) (PD-1/VEGF-A)

Target
PD-1/VEGF-A
Molecular classification
Receptor, Growth factor
01

Overview

Programmed cell death protein 1 (PD-1) and Vascular endothelial growth factor A (VEGF-A) are critical therapeutic targets in oncology that regulate immune evasion and tumor angiogenesis, respectively. PD-1 is an inhibitory checkpoint receptor expressed on the surface of T cells; its interaction with ligands PD-L1 and PD-L2 suppresses T-cell activation and allows tumors to escape immune surveillance (Summit Therapeutics, 2024). VEGF-A is a potent growth factor secreted by tumor cells to stimulate the formation of new blood vessels, ensuring nutrient supply and creating a hypoxic, immunosuppressive microenvironment (Akeso, 2024). Ivonescimab (AK112) is a first-in-class bispecific antibody designed to bind both PD-1 and VEGF-A with high affinity. This dual-targeting approach aims to synergistically restore anti-tumor immune responses while normalizing tumor vasculature, potentially overcoming resistance to standard checkpoint inhibitors (Journal of Hematology & Oncology, 2023). Clinical development of drugs targeting this dual axis, such as Ivonescimab, has shown significant promise in treating non-small cell lung cancer (NSCLC), particularly in patients with EGFR mutations or those who have progressed on prior therapies (ClinicalTrials.gov, 2024).

Other names
PDCD1CD279SLEB2hPD-1VEGFAVPFVascular permeability factor
02

Mechanism of action

Simultaneous blockade of the PD-1/PD-L1 immune checkpoint and the VEGF/VEGFR angiogenic pathway to enhance anti-tumor immunity and inhibit tumor vascularization.

03

Biological functions

Immune responseAngiogenesisSignal transductionCell proliferation
04

Disease associations

Cancer
05

Safety considerations

Immune-related adverse events (irAEs)HypertensionProteinuriaHemorrhageGastrointestinal perforationWound healing complications
06

Interacting drugs

Ivonescimab

2 more in the full profile.

07

Biomarkers

PD-L1 expressionVEGF-A levelsEGFR mutation statusTumor Mutational Burden (TMB)

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