Folate receptor alpha E39 peptide-HLA-A*02:01 complex (FRα E39/HLA-A2)

Folate receptor alpha (FRα) is a cell-surface glycoprotein that mediates the transport of folate into cells and is significantly overexpressed in several malignancies, including ovarian, lung, and breast cancers (PMID: 24651535). The E39 peptide is a specific immunogenic epitope with the sequence EIWTHSTGY, derived from FRα residues 191–199 (PMID: 10506499). This peptide is naturally processed and presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule on the surface of tumor cells. The resulting peptide-MHC complex acts as a tumor-associated antigen that can be recognized by the T-cell receptors (TCR) of CD8+ cytotoxic T-lymphocytes (PMID: 16140943). Therapeutic approaches, such as the E39 peptide vaccine, are designed to prime the immune system to identify and destroy FRα-expressing tumor cells. Because FRα expression is highly restricted in normal tissues, targeting the E39/HLA-A2 complex offers a strategy for high tumor specificity and reduced off-target toxicity (PMID: 20406354). Clinical development has focused on using this target for vaccine-based prevention of disease recurrence in patients with high-risk FRα-expressing tumors (NCT01580696). This target represents a precision medicine approach, requiring patients to be both HLA-A2 positive and have FRα-expressing tumors.

Other names

E39 peptideFolate receptor 1 (191-199) peptideEIWTHSTGY peptideFOLR1-derived peptide E39Folate receptor alpha-derived peptide E39FRα(191-199)

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) response against tumor cells presenting the E39 peptide on HLA-A2.