Estrogen receptor 1 mutant neoantigen-MHC complex (ESR1-neoAg-MHC)

Estrogen receptor 1 (ESR1) mutant neoantigens presented on MHC complexes are highly specific targets for immunotherapy in advanced breast cancer. Mutations in the ESR1 gene, such as Y537S and D538G, frequently emerge under the selective pressure of aromatase inhibitor therapy, leading to constitutive, ligand-independent receptor activity and endocrine resistance (Toy et al., 2013, Nature Genetics). These somatic mutations result in the synthesis of neoantigenic peptides that are processed and displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily HLA-A*02:01. Because these mutant sequences are not present in the germline, they are recognized as foreign by the immune system, making them ideal targets for T-cell receptor (TCR) engineered T-cell therapies and personalized cancer vaccines (Schneeweiss et al., 2021, Journal of Clinical Oncology). By targeting the peptide-MHC complex, therapeutic interventions can selectively eliminate resistant tumor clones while sparing healthy tissues that express only the wild-type estrogen receptor. This approach represents a precision medicine strategy to address the clinical challenge of metastatic, hormone-receptor-positive breast cancer that has progressed on standard endocrine therapies.

Other names

ESR1 mutation-derived neoantigensHLA-presented ESR1 mutant peptidesEstrogen receptor alpha mutant neoantigensESR1 pMHC complex

Selective recognition of mutant ESR1 peptides presented by MHC molecules by engineered T-cell receptors (TCRs) or vaccines to induce a cytotoxic immune response against tumor cells.