Mutant CTNNB1-derived neoantigen peptides presented by HLA (Mutant CTNNB1-HLA neoantigen)

Mutant CTNNB1-derived neoantigen peptides presented by HLA are tumor-specific antigens arising from somatic mutations in the CTNNB1 gene, which encodes the beta-catenin protein. These mutations, frequently occurring at hotspots such as S33, S37, T41, and S45, lead to the constitutive activation of the Wnt signaling pathway, a key driver in various malignancies including hepatocellular carcinoma, colorectal cancer, and endometrial cancer (Hwang et al., JBC, 2020; Eggebø et al., Nature Immunology, 2024). When these mutant proteins are processed intracellularly, the resulting neopeptides are presented on the cell surface by specific Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*02:01, HLA-A*24:02, and HLA-A*03:01 (Eggebø et al., Nature Immunology, 2024; Hwang et al., JBC, 2020). Because these neoantigens are absent in normal tissues, they represent highly specific targets for precision immunotherapies, including TCR-engineered T cells (TCR-T), TCR-mimic antibodies, and personalized vaccines (University of Oslo, News-Medical, 2024). Therapeutic strategies aim to leverage the immune system's ability to recognize these "non-self" peptides to selectively eliminate cancer cells while sparing healthy tissue. For instance, TCRs like TCRA2-2 and TCRA24 have been developed to target the S37F mutation in the context of HLA-A*02:01 and HLA-A*24:02, respectively (Eggebø et al., Nature Immunology, 2024). However, challenges such as HLA downregulation and low antigen density on the tumor surface remain significant hurdles for clinical efficacy (ResearchGate, 2024).

Other names

Mutant beta-catenin neoantigenCTNNB1 mutation-associated neoantigenMANA-CTNNB1CTNNB1-S37F neoantigenCTNNB1-S45F neoantigenCTNNB1-S33C neoantigenCTNNB1-T41A neoantigenpHLA-CTNNB1

T cell-mediated cytotoxicity via specific recognition of the mutant peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-mimic antibodies, leading to the selective destruction of tumor cells harboring CTNNB1 mutations.