Folate receptor alpha (191-199) peptide-HLA-A*02:01 complex (FRα E39/HLA-A2)

The HLA-A2-presented FRα-derived E39 epitope is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. It consists of a 9-amino acid sequence (EIWTHSYKV) derived from the Folate Receptor alpha (FRα) protein, which is highly overexpressed in various epithelial malignancies, particularly ovarian and endometrial cancers (Peoples et al., 1999, Clin. Cancer Res.). This specific epitope is presented on the cell surface by the HLA-A*02:01 allele, allowing it to be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Kim et al., 1999, Cancer). Therapeutic strategies targeting this complex primarily involve peptide vaccines, such as E39 and its modified version E39', which are designed to stimulate a robust anti-tumor immune response (NCT01580696). These vaccines aim to prevent disease recurrence by training the immune system to identify and destroy residual cancer cells expressing the FRα protein (Sabbatini et al., 2018, Clin. Cancer Res.). Because FRα expression is significantly higher in malignant tissues compared to normal tissues, the E39 epitope serves as a viable target for minimizing systemic toxicity. Clinical trials have investigated these vaccines in patients with folate receptor-expressing cancers who are in clinical remission but at high risk of relapse (Greene et al., 2016, Cancer Immunol. Immunother.).

Other names

E39 epitopeFRα (191-199)EIWTHSYKV peptideFolate receptor alpha-derived E39 peptideHLA-A*02:01-restricted FRα epitope

Vaccine-mediated stimulation of the immune system to produce E39-specific CD8+ T cells that recognize and lyse HLA-A2+ tumor cells expressing Folate receptor alpha.