HLA-A*02:01-presented CircFam53B-219aa peptide complex (HLA-A*02:01/CircFam53B-219aa)

The target is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 allele presenting epitopes derived from the CircFam53B-219aa protein. CircFam53B-219aa is a novel, tumor-specific protein translated from a circular RNA (circFAM53B) via an internal ribosome entry site (IRES) (Zhang et al., 2021, Molecular Cancer). This protein is significantly overexpressed in glioblastoma and other malignancies, where it functions as an oncogene by activating the Wnt/beta-catenin signaling pathway to promote tumor cell proliferation and invasion (Zhang et al., 2021, Molecular Cancer). Because the protein sequence is derived from a circularized RNA junction, it contains unique amino acid sequences not found in the canonical linear FAM53B protein, making it a highly specific neoantigen for immunotherapy. Therapeutic strategies targeting this complex include TCR-engineered T cells (TCR-T) and neoantigen-based vaccines designed to induce a CD8+ T-cell mediated cytotoxic response against cancer cells (Wang et al., 2022, Frontiers in Immunology). By targeting a circRNA-derived neoantigen, these therapies aim to achieve high tumor specificity and minimize damage to healthy tissues that do not express the circular isoform.

Other names

CircFam53B-219aa neoantigenFAM53B-219aacircFAM53B-encoded proteinhsa_circ_0001944-derived proteinHLA-A*02:01-CircFam53B complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ T cells triggers cytotoxic T-lymphocyte (CTL) activity, leading to the selective lysis of tumor cells expressing the CircFam53B-219aa protein.