Neoantigen-specific T-cell receptor (NeoTCR) (NeoTCR)

Neoantigen-specific T-cell receptors (NeoTCRs) are a class of engineered or naturally occurring receptors that recognize unique peptides derived from tumor-specific somatic mutations presented by Major Histocompatibility Complex (MHC) molecules (Nature, 2022). Unlike traditional T-cell therapies that target shared tumor-associated antigens, NeoTCRs target "neoantigens" which are entirely absent from the normal human proteome, significantly reducing the risk of off-target toxicity (Science, 2021). These receptors are central to personalized TCR-T cell therapies, where a patient's own T-cells are modified to express a TCR specifically tailored to their tumor's unique genetic profile (Cell, 2020). Upon binding to the neoantigen-MHC complex, the NeoTCR initiates a signaling cascade that leads to T-cell proliferation and the targeted destruction of the cancer cell via cytotoxic mechanisms (Journal of Clinical Investigation, 2019). This technology is currently being evaluated in clinical trials for various solid tumors, offering a highly precise treatment modality for patients with advanced malignancies (NEJM, 2016). Despite their potential, the clinical application of NeoTCRs faces hurdles such as the requirement for complex, patient-specific manufacturing and the potential for tumor resistance through the loss of HLA expression (Nature Communications, 2023).

Other names

Neoantigen-reactive T-cell receptorMutation-specific T-cell receptorPatient-specific TCRNeoepitope-specific TCR

Neoantigen-specific T-cell receptors recognize and bind to specific neoepitope-HLA complexes on tumor cells, triggering T-cell activation, the release of cytotoxic granules (perforin/granzymes), and the production of cytokines (IFN-gamma), leading to selective tumor cell lysis (Nature, 2022).