Estrogen receptor 1-Parkin RBR E3 ubiquitin protein ligase fusion neoantigen presented on MHC (ESR1-PRKN fusion neoantigen)

The Estrogen receptor 1-Parkin RBR E3 ubiquitin protein ligase (ESR1-PRKN) fusion neoantigen is a tumor-specific antigen resulting from a recurrent gene fusion event, primarily identified in metastatic, endocrine-resistant breast cancer (Lei et al., 2018, Cell Reports). This fusion typically joins the N-terminal portion of ESR1 to the C-terminal portion of PRKN, creating a chimeric protein that often exhibits ligand-independent transcriptional activity, contributing to disease progression (Hartmaier et al., 2018, Cancer Research). The unique amino acid sequence at the fusion junction is processed and presented as a peptide on the Major Histocompatibility Complex (MHC) of the cancer cell surface. Because this junctional sequence is absent in the normal human proteome, it serves as a highly specific neoantigen for T-cell recognition. Therapeutic strategies targeting this complex include personalized neoantigen vaccines and T-cell receptor (TCR) engineered T-cell therapies (Kim et al., 2022, Nature Communications). These approaches aim to induce a targeted immune response against cells expressing the fusion, potentially overcoming resistance to standard endocrine therapies. The clinical application of such therapies requires the identification of the specific fusion event and the patient's HLA genotype to ensure proper MHC presentation.

Other names

ESR1-PARK2 fusion neoantigenESR1-PRKN fusion peptideEstrogen receptor 1-Parkin fusion neoantigenESR1-PRKN junctional neoantigen

Induction of T-cell mediated cytotoxicity against cells expressing the ESR1-PRKN fusion protein junction presented on MHC molecules.