Androgen receptor ligand-binding domain-derived peptide:MHC class I complex (AR-LBD peptide:MHC-I)

The androgen receptor ligand-binding domain-derived peptide:MHC class I complex is a tumor-associated antigen presented on the surface of prostate cancer cells. The androgen receptor (AR) is a nuclear receptor that drives the progression of prostate cancer, especially in its castration-resistant form (Olson et al., 2017, Frontiers in Oncology). Peptides from the AR ligand-binding domain (LBD) are processed and displayed by MHC class I molecules, such as HLA-A*02:01, making them visible to the cellular immune system (McNeel et al., 2014, Cancer Research). This complex is the primary target for immunotherapies like the pTVG-AR DNA vaccine and T-cell receptor (TCR) engineered T-cells, which seek to trigger a cytotoxic T-cell response against malignant cells (NCT02411708). By focusing on the LBD, these therapies target a region of the receptor that is often preserved or overexpressed in advanced disease. However, the use of this target requires careful patient screening for specific HLA types to ensure the peptide can be properly presented. Potential safety concerns include 'on-target, off-tumor' effects in normal tissues that express the androgen receptor, although the prostate itself is often the primary site of expression. Additionally, tumors may attempt to evade treatment by downregulating MHC expression or through other immune checkpoint mechanisms.

Other names

AR-LBD pMHC complexAndrogen receptor peptide-HLA complexAR-LBD/HLA-A*02:01 complexAR-LBD antigen

Induction of antigen-specific CD8+ T-cell mediated cytotoxicity against cells presenting AR-LBD peptides.