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Epidermal growth factor receptor pathway substrate 8 peptide-HLA-A*02:01 complex (Eps8-HLA-A2 complex)

Target
Eps8-HLA-A2 complex
Molecular classification
MHC class I-peptide complex, Antigen-presenting complex, Major Histocompatibility Complex (MHC)
01

Overview

The Epidermal growth factor receptor pathway substrate 8 (Eps8) peptide-HLA-A*02:01 complex is a tumor-associated antigen (TAA) target presented on the surface of various malignant cells. Eps8 is a signaling protein that regulates actin remodeling and is frequently overexpressed in solid tumors, including pancreatic, colorectal, and breast cancers, as well as some leukemias (PMID: 18263614, 28415615). In these cells, Eps8 is proteolytically processed into short peptides, which are then loaded onto HLA-A*02:01 molecules and transported to the cell surface (PMID: 20683003). This specific peptide-MHC complex serves as a molecular signature that can be recognized by the immune system, specifically by cytotoxic T lymphocytes (CTLs) via their T-cell receptors (TCRs). Therapeutic strategies targeting this complex include peptide-based vaccines designed to elicit an endogenous immune response and adoptive cell therapies, such as TCR-engineered T cells, which provide a direct means of eliminating Eps8-positive tumor cells (PMID: 20683003, 21814175). Because Eps8 expression is significantly higher in tumor tissues compared to most normal tissues, it represents a promising target for precision immunotherapy.

Other names
Eps8-derived peptide-MHC complexHLA-A*02:01/Eps8 complexEps8-HLA-A2Peptide-HLA-A2.1 complexes presenting Eps8
02

Mechanism of action

Binding of specific T-cell receptors (TCRs) or TCR-like antibodies to the peptide-MHC complex on the tumor cell surface, triggering cytotoxic T-lymphocyte (CTL) activation and subsequent lysis of the target cell.

03

Biological functions

Antigen presentationImmune recognitionT-cell activationImmune surveillance
04

Disease associations

CancerSolid tumorsAcute myeloid leukemiaPancreatic cancerColorectal cancer
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Safety considerations

On-target off-tumor toxicity (due to low-level Eps8 expression in some normal tissues)HLA restriction (limited to HLA-A*02:01 positive patients)Antigen escape (downregulation of HLA or Eps8 by tumor cells)
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Interacting drugs

Eps8-derived peptide vaccines

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeEps8 protein expressionEps8 mRNA levels

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