Target intelligence / Profile preview

Prostate-specific antigen (154–163) peptide-HLA-A*02:01 complex (PSA:154-163/HLA-A2)

Target
PSA:154-163/HLA-A2
Molecular classification
Peptide-MHC class I complex, Tumor-associated antigen (TAA), Antigen
01

Overview

The PSA:154–163–HLA-A2 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of prostate cancer cells. It consists of a 10-amino acid epitope (VISNDVCAQV) derived from the Prostate-Specific Antigen (PSA, also known as KLK3), which is processed and presented by the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule (Correale et al., 1997). This complex serves as a highly specific target for immunotherapy because PSA is significantly overexpressed in prostate adenocarcinoma compared to other tissues (He et al., 2020). Therapeutic strategies targeting this complex include TCR-engineered T cells and TCR-like antibodies, which are designed to bypass the limitations of traditional CAR-T cells by targeting intracellularly derived proteins presented on the cell surface (Wittman et al., 2006). While the target is highly specific to the prostate, the primary safety concern is the potential for 'on-target, off-tumor' effects on healthy prostate tissue, which is generally considered an acceptable risk in the treatment of advanced or metastatic prostate cancer.

Other names
PSA(154-163)/HLA-A*02:01VISNDVCAQV-HLA-A2 complexKLK3(154-163)-HLA-A2PSA peptide 154-163 presented by HLA-A2
02

Mechanism of action

Induction of T-cell mediated cytotoxicity through the specific recognition of the VISNDVCAQV peptide presented by HLA-A*02:01 molecules on the surface of tumor cells by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies.

03

Biological functions

Antigen presentationT-cell recognitionImmune surveillance
04

Disease associations

Prostate cancerMetastatic castration-resistant prostate cancer (mCRPC)
05

Safety considerations

On-target, off-tumor toxicity (potential destruction of normal prostate epithelium)Cross-reactivity with similar peptide sequences in healthy tissuesCytokine release syndrome (CRS) associated with T-cell activation
06

Interacting drugs

PSA-peptide vaccines (e.g., VISNDVCAQV-based vaccines)

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypePSA (KLK3) expression in tumor tissueSerum PSA levels

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