HLA-A*02:01-restricted Folate Receptor alpha peptide complex (HLA-A2/FRα complex)

The HLA-A*02:01-restricted Folate Receptor alpha (FRα) peptide complex is a specific molecular target consisting of the Human Leukocyte Antigen A*02:01 molecule presenting immunogenic peptides derived from the Folate Receptor alpha protein, also known as Folate Binding Protein (FBP) (Kim et al., 2012). FRα is a glycosylphosphatidylinositol-anchored glycoprotein that is highly overexpressed in various epithelial malignancies, particularly ovarian, lung, and breast cancers, while maintaining limited expression in normal tissues (Snyder et al., 2016). This differential expression makes the HLA-A2/FRα peptide complex an attractive target for T-cell-based immunotherapies, including peptide vaccines and T-cell receptor (TCR) engineered T-cell therapies (Peoples et al., 2005). Drugs targeting this complex, such as the E39 peptide vaccine, aim to harness the cellular immune system to recognize and eliminate malignant cells by binding specifically to the peptide-MHC interface (Greene et al., 2016). Clinical development has focused on peptides like E39 (FRα 191–199) to stimulate endogenous anti-tumor immunity or to serve as the recognition element for synthetic receptors (Schmitt et al., 2015). The therapeutic efficacy of targeting this complex depends on both the presence of the HLA-A*02:01 allele and the sufficient expression of the FRα protein on the tumor cell surface.

Other names

HLA-A2 presenting FRα/FBP-derived epitopesHLA-A*02:01/FOLR1 peptide complexFolate receptor alpha-derived MHC-I complexE39/HLA-A2 complexFBP-derived HLA-A2 restricted epitope

Induction of peptide-specific CD8+ cytotoxic T lymphocyte (CTL) responses and direct T-cell mediated lysis of tumor cells presenting the FRα-derived epitopes.