Tumor neoantigen-specific T-cell receptor (NeoTCR)

Tumor neoantigen-specific T-cell receptors (NeoTCRs) are engineered or naturally derived receptors designed to recognize unique, patient-specific mutations (neoantigens) presented by Major Histocompatibility Complex (MHC) molecules on tumor cells. Unlike receptors targeting shared tumor-associated antigens, NeoTCRs focus on "non-self" epitopes that arise from somatic mutations, which significantly reduces the risk of off-target toxicity against healthy tissues (Goyal et al., 2022, Nature). These receptors are the core component of personalized TCR-T cell therapies, where a patient's autologous T-cells are genetically modified to express a specific NeoTCR before being expanded and re-infused (Robbins et al., 2014, Science). Upon re-infusion, these engineered cells migrate to the tumor microenvironment and initiate a targeted cytotoxic response through the release of perforins, granzymes, and pro-inflammatory cytokines (Draper et al., 2023, JITC). This approach is particularly effective for treating solid tumors with high mutational burdens, such as melanoma and lung cancer, which may be resistant to standard immunotherapies (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Despite their potential, NeoTCR therapies require complex, individualized manufacturing processes and face challenges such as tumor immune escape via HLA downregulation or antigen loss (Schuster et al., 2021, Frontiers in Immunology).

Other names

Neoantigen-reactive T-cell receptorNeoepitope-specific T-cell receptorMutation-specific T-cell receptorNeoantigen-specific TCR

Adoptive cell transfer of T-cells engineered to express a specific NeoTCR that recognizes mutant peptides presented by MHC molecules, leading to targeted tumor cell lysis.