Patient-specific neoantigen-restricted T-cell receptor (NeoTCR)

Patient-specific neoantigen-restricted T-cell receptors (NeoTCRs) are highly specialized receptors engineered to recognize unique mutations, or neoantigens, found exclusively within an individual patient's tumor (Foy et al., Nature, 2023). These neoantigens are processed and presented as peptides by the Major Histocompatibility Complex (MHC) on the surface of malignant cells, serving as precise targets for the immune system (Tran et al., Science, 2014). In therapeutic contexts, such as NeoTCR-T cell therapy, a patient's own T cells are genetically modified to express these specific receptors, enabling a targeted attack against solid tumors while sparing healthy tissue (Parkhurst et al., Clinical Cancer Research, 2019). This personalized approach addresses the limitations of targeting shared tumor antigens, which can lead to off-target toxicities in normal organs. The biological function of the NeoTCR involves the initiation of T-cell signaling and cytotoxic activity upon binding to the specific neoantigen-MHC complex. Despite their potential, the success of NeoTCR-based therapies depends on the accurate identification of immunogenic mutations and the ability of the engineered cells to persist within the immunosuppressive tumor microenvironment (Blass & Ott, Nature Reviews Clinical Oncology, 2021).

Other names

Neoantigen-specific T-cell receptorPersonalized TCRNeoTCR-TMutation-specific TCRNeoantigen-restricted TCR

Binding of the engineered T-cell receptor to a specific neoantigen peptide-MHC complex on the tumor cell surface, triggering the formation of an immunological synapse, T-cell degranulation, and subsequent apoptosis of the target cancer cell.