Vascular endothelial growth factor receptor 1-specific T-cell receptor (VEGFR1-specific TCR) (VEGFR1-specific TCR)

The Vascular endothelial growth factor receptor 1-specific T-cell receptor (VEGFR1-specific TCR) is a specialized protein complex found on the surface of CD8+ cytotoxic T lymphocytes that specifically recognizes peptides derived from VEGFR1 (also known as Flt-1) [1]. VEGFR1 is a receptor tyrosine kinase that plays a pivotal role in angiogenesis and is significantly overexpressed on the vascular endothelial cells of various solid tumors, as well as on certain cancer cells [2]. By binding to VEGFR1 peptides presented by Major Histocompatibility Complex (MHC) class I molecules, this TCR enables T cells to selectively target and destroy tumor-associated blood vessels, thereby inhibiting tumor growth by cutting off its blood supply [1, 3]. Therapeutic interventions targeting this pathway include peptide-based vaccines designed to induce and expand endogenous VEGFR1-specific CTLs, as well as adoptive cell therapies using T cells engineered to express high-affinity VEGFR1-specific TCRs [4]. Clinical studies have explored these approaches in malignancies such as pancreatic, colorectal, and renal cell carcinomas, often utilizing specific HLA-restricted peptides like VEGFR1-1084 [5]. While generally well-tolerated, potential safety concerns include the disruption of normal physiological angiogenesis and the risk of systemic inflammatory responses [4, 5].

Other names

Flt-1-specific T-cell receptorVEGFR1-targeted TCRT-cell receptor on VEGFR1-specific CD8+ cytotoxic T lymphocytesVascular endothelial growth factor receptor 1-specific TCR

The TCR recognizes specific VEGFR1-derived peptides presented by MHC Class I molecules (e.g., HLA-A*24:02) on the surface of target cells, such as tumor-associated endothelial cells. This recognition triggers T-cell activation, leading to the release of cytotoxic molecules like perforin and granzymes, which induce apoptosis in the target cells and inhibit tumor angiogenesis.