Ephrin type-A receptor 2-derived peptide-MHC complex (EphA2 pMHC)

Ephrin type-A receptor 2 (EphA2)-derived peptide epitopes presented on tumor Major Histocompatibility Complex (MHC) molecules are critical targets for cancer immunotherapy, particularly in high-grade gliomas (Hatano et al., 2005, PMID: 15642759). EphA2 is a receptor tyrosine kinase that is significantly overexpressed in glioblastoma and other malignancies, where it promotes tumor cell proliferation, invasion, and neoangiogenesis (Wykosky et al., 2005, PMID: 16140943). Intracellular processing of the EphA2 protein generates specific peptide fragments, such as the HLA-A2-restricted EphA2 883-891 epitope, which are displayed on the cell surface in complex with MHC class I molecules (Alves et al., 2003, PMID: 12855651). These complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making them ideal candidates for therapeutic vaccines like IMA950 and engineered T-cell therapies (Rampling et al., 2016, PMID: 27528712). By targeting these specific pMHC complexes, clinicians aim to induce a robust and selective anti-tumor immune response while minimizing damage to healthy tissues that express lower levels of the parent protein. However, challenges such as antigen loss and the immunosuppressive tumor microenvironment remain significant hurdles in achieving durable clinical efficacy (Dutoit et al., 2012, PMID: 22431914).

Other names

EphA2-derived glioma-associated antigenEphA2 HLA-restricted epitopeEphA2 883-891 peptideEphA2-GAAEphA2-derived T-cell epitope

Induction of cytotoxic T-lymphocyte (CTL) responses against tumor cells presenting EphA2-derived peptides on MHC molecules, leading to targeted cell lysis.