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

The HLA-A2-E39 complex is a peptide-major histocompatibility complex (pMHC) that serves as a specific target for cancer immunotherapy, particularly in gynecological malignancies (Greene et al., 2016). The E39 peptide (EIWTHSTNY) is a 9-amino acid epitope derived from Folate Receptor Alpha (FRα), a protein that is highly overexpressed in ovarian, endometrial, and breast cancers but has limited distribution in normal tissues (Kim et al., 1999; O'Shannessy et al., 2012). When presented by the HLA-A*02:01 molecule, this complex is recognized by the T-cell receptors of specific cytotoxic T lymphocytes (CTLs). Therapeutic strategies, such as the E39 and E39-7 peptide vaccines, aim to stimulate the patient's immune system to generate these CTLs to eliminate residual disease and prevent recurrence (Gall et al., 2017). The complex is a key focal point for developing precision immunotherapies that leverage the high tumor-specificity of FRα-derived antigens. Clinical studies have primarily evaluated these interventions in the adjuvant setting for patients who are in clinical remission but at high risk of relapse (NCT01580696). Monitoring of the immune response typically involves measuring the frequency of E39-specific CD8+ T cells in the peripheral blood. Overall, the HLA-A2-E39 complex represents a promising target for reducing the risk of relapse in gynecological malignancies.

Other names

E39 peptideFolate receptor alpha (191-199) peptideFRα-E39EIWTHSTNY peptideE39-HLA-A2 complexFolate receptor alpha peptide vaccine

The E39 vaccine is an active immunotherapy that induces the expansion of endogenous CD8+ cytotoxic T lymphocytes (CTLs) specific for the E39 peptide-HLA-A2 complex (Greene et al., 2016). These CTLs recognize the EIWTHSTNY peptide presented by HLA-A*02:01 on the surface of tumor cells. Upon binding, the CTLs trigger tumor cell lysis through the release of cytotoxic molecules and cytokines (Gall et al., 2017).