T-cell receptor specific for ODC1-derived neoantigen peptide–HLA complex (ODC1-specific TCR)

The T-cell receptor (TCR) specific for ODC1-derived neoantigen peptide–HLA complex is a specialized immune receptor used in TCR-engineered T-cell (TCR-T) therapy to target cancer cells. It specifically recognizes neoantigens derived from mutations in the Ornithine decarboxylase 1 (ODC1) protein, such as the Q129L mutation, when presented by Human Leukocyte Antigen (HLA) molecules (Swartz et al., 2018). ODC1 is a critical enzyme in polyamine biosynthesis and is often overexpressed or mutated in aggressive tumors like glioblastoma and breast cancer (Schultz et al., 2018). By engineering a patient's T-cells to express this TCR, the immune system can be redirected to identify and destroy tumor cells with high precision. This recognition triggers T-cell activation, leading to the release of cytotoxic molecules like granzymes and perforins that induce apoptosis in the target cells (Swartz et al., 2021). Unlike traditional therapies, TCR-T cells can penetrate the blood-brain barrier and address the immunosuppressive microenvironment of brain tumors. This target is particularly valuable for treating tumors with low mutational burden where few other neoantigens are available. Ongoing research focuses on optimizing TCR affinity and overcoming T-cell exhaustion to enhance the durability of the anti-tumor response (Burrack et al., 2019). Clinical trials are evaluating vaccines and TCR-based strategies targeting ODC1 in glioblastoma patients (NCT04808245).

Other names

ODC1-specific T-cell receptorTCR specific for ODC1 neoantigenODC1-Q129L-specific TCROrnithine decarboxylase 1-specific TCRODC1-TCR

The TCR-engineered T-cells express a specific receptor that recognizes the ODC1-derived neoantigen peptide presented by HLA molecules on tumor cells. This recognition leads to the formation of an immunological synapse, T-cell activation, and the release of cytotoxic granules (perforin and granzymes) and cytokines (IFN-gamma, TNF-alpha), resulting in the targeted lysis of the cancer cells.