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Vascular endothelial growth factor receptor 1 (VEGFR1)-derived peptide presented by HLA class I (VEGFR1 peptide-HLA complex)

Target
VEGFR1 peptide-HLA complex
Molecular classification
Peptide-MHC complex, Antigen
01

Overview

The Vascular endothelial growth factor receptor 1 (VEGFR1)-derived peptide presented by HLA class I is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy (Wada et al., 2005, Cancer Research). VEGFR1, also known as FLT1, is a tyrosine kinase receptor significantly overexpressed in the vascular endothelial cells of tumor tissues and certain cancer cells, where it plays a critical role in tumor-induced angiogenesis (Miyazawa et al., 2010, Cancer Science). When VEGFR1 proteins are degraded within the cell, specific peptide fragments, such as the VEGFR1-1084 epitope (SYGVLLWEIF), are loaded onto HLA class I molecules—most commonly HLA-A*24:02—and transported to the cell surface. This complex acts as a beacon for the immune system, specifically for cytotoxic T lymphocytes (CTLs) that can recognize the epitope via their T-cell receptors. Therapeutic strategies targeting this complex include peptide vaccines and TCR-engineered T-cell therapies designed to induce a robust immune response against the tumor vasculature (OncoTherapy Science, Pipeline). By destroying the endothelial cells that support tumor growth, these therapies aim to starve the tumor of nutrients and oxygen. Clinical studies have explored these vaccines in various malignancies, including pancreatic and colorectal cancers, often demonstrating the induction of specific CTL responses with a manageable safety profile.

Other names
VEGFR1-1084 peptide-HLA complexFLT1-derived peptide-MHC complexVEGFR1 epitope-HLA-A*24:02 complexVEGFR1-1084/HLA-A24
02

Mechanism of action

Induction of peptide-specific cytotoxic T lymphocytes (CTLs) that recognize and lyse VEGFR1-expressing cells, primarily tumor-associated endothelial cells, thereby inhibiting tumor angiogenesis.

03

Biological functions

Antigen presentationImmune responseAngiogenesis regulation
04

Disease associations

CancerSolid tumorsPancreatic cancerColorectal cancerRenal cell carcinoma
05

Safety considerations

On-target off-tumor toxicity to normal vascular endothelial cellsInjection site reactionsSystemic inflammatory responsePotential for impaired wound healing
06

Interacting drugs

VEGFR1-1084 peptide vaccine

1 more in the full profile.

07

Biomarkers

HLA-A*24:02 genotypeVEGFR1 expression levelsPeptide-specific CTL frequency

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