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

Patient-specific neoantigen-specific T-cell receptors (NeoTCRs) are engineered receptors designed to recognize unique mutations, or neoantigens, present exclusively in an individual patient's tumor. Unlike traditional CAR-T cells that recognize surface proteins, NeoTCRs identify intracellular proteins processed and presented as peptides on the Major Histocompatibility Complex (MHC) (Schumacher & Schreiber, Science 2015). This approach allows for highly precise targeting of the mutanome, significantly reducing the risk of off-tumor toxicity compared to shared-antigen therapies. In therapeutic applications, T cells are isolated from a patient, genetically modified to express these personalized TCRs, and re-infused to mount a potent, specific immune response (Mandl et al., Nature 2022). This technology is particularly relevant for solid tumors, where high mutational loads provide a diverse array of potential targets. However, challenges remain regarding the complex manufacturing process and the potential for tumor escape through HLA downregulation (Tran et al., Science 2014).

Other names

Neoantigen-specific T-cell receptorPersonalized T-cell receptorTumor-specific T-cell receptorNeo-TCRMutation-specific T-cell receptor

Engineered T-cells express a patient-specific TCR that recognizes unique somatic mutations (neoantigens) presented as peptides on the Major Histocompatibility Complex (MHC) of tumor cells. This binding triggers the formation of an immunological synapse, leading to the release of perforins and granzymes, which induce apoptosis in the target cancer cell (Nature, 2022; Science, 2015).