T-cell receptor recognizing neoantigen peptide-HLA complex (NeoTCR)

T-cell receptors (TCRs) recognizing neoantigen peptide-HLA complexes are a specialized class of immune receptors that target unique, mutation-derived peptides presented by Human Leukocyte Antigen (HLA) molecules on the surface of cancer cells (Schumacher & Schreiber, 2015, Science). These neoantigens arise from somatic mutations—such as point mutations, insertions, or deletions—that are entirely absent in healthy tissues, providing a high degree of tumor specificity and reducing the risk of autoimmune reactions (Blankenstein et al., 2015, Nature Reviews Cancer). In the context of cancer immunotherapy, these TCRs are utilized in TCR-engineered T-cell (TCR-T) therapies, where a patient's T-lymphocytes are genetically modified to express a TCR specific to their tumor's unique neoantigen profile (Klebanoff et al., 2016, Nature Medicine). Upon binding to the neoantigen-HLA complex, the TCR initiates a signaling cascade that activates the T-cell, leading to the secretion of pro-inflammatory cytokines and the release of cytotoxic granules to destroy the malignant cell. This personalized approach is particularly effective for solid tumors with high mutational burdens, such as melanoma and lung cancer, where traditional therapies may fail. However, the clinical application of these TCRs faces challenges, including the need for precise neoantigen identification, the requirement for specific HLA matching, and the potential for off-target cross-reactivity with similar self-peptides (Linette et al., 2013, Blood).

Other names

Neoantigen-specific T-cell receptorMutation-specific TCRNeoantigen-reactive TCRNeoTCR

Adoptive T-cell therapy where T-cells are engineered to express TCRs that bind specifically to tumor-specific neoantigen-HLA complexes, triggering T-cell mediated cytotoxicity.