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

A neoantigen-specific T cell receptor (TCR) is a specialized immune receptor engineered or isolated to recognize unique, patient-specific mutations (neoantigens) presented by MHC class I molecules on the surface of tumor cells (Frontiers in Immunology, 2022). Unlike traditional TCRs that target shared tumor-associated antigens, neoTCRs are highly specific to somatic mutations not found in healthy tissues, which significantly reduces the risk of on-target/off-tumor toxicity (NIH, 2025). These receptors are the fundamental component of neoantigen-specific TCR-T cell therapy, where a patient's T cells are genetically modified to express the neoTCR, expanded ex vivo, and reinfused to mount a personalized immune response (Creative Biolabs, 2022). The biological function of the neoTCR involves the precise recognition of the peptide-MHC complex, which triggers a signaling cascade leading to T cell activation, proliferation, and the release of cytotoxic molecules like granzymes and perforins to destroy the cancer cell (Therapeutic Nanomedicine, 2023). In clinical development, neoTCRs are being investigated for various solid tumors and hematological malignancies, utilizing advanced genomic sequencing and bioinformatics to identify the most immunogenic mutation-HLA pairs for each individual (BMJ, 2025).

Other names

Neoantigen-reactive T cell receptorMutation-specific T cell receptorNeoTCRTumor-specific T cell receptorNeoantigen-specific αβTCR

Recognition of patient-specific neoantigen peptides presented by MHC class I molecules, leading to T cell activation, cytokine release, and targeted lysis of tumor cells.