T-cell receptor recognizing patient-specific neoantigen peptide-MHC complexes (NeoTCR)

The T-cell receptor (TCR) recognizing patient-specific neoantigen peptide-MHC complexes is a specialized immune receptor utilized in personalized adoptive cell therapies. Neoantigens are novel, non-self peptides derived from somatic mutations unique to an individual's tumor, which are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Foy et al., Nature, 2023). Unlike shared tumor antigens, neoantigens are not subject to central thymic tolerance, allowing for the selection of high-affinity TCRs that can robustly distinguish malignant cells from healthy tissue (Tran et al., Science, 2014). In clinical practice, these TCRs are identified via whole-exome sequencing and bioinformatic prediction, then validated for their ability to trigger T-cell responses. Once a suitable TCR is identified, it is transduced into the patient's peripheral blood lymphocytes to create a customized "living drug" capable of infiltrating solid tumors and executing a precise cytotoxic attack. This therapeutic strategy is particularly promising for patients with high mutational burden cancers who have failed standard checkpoint inhibitor therapies (Yarchoan et al., Nature Reviews Cancer, 2017). The interaction between the engineered TCR and the neoantigen-MHC complex is highly specific to the patient's unique tumor profile and HLA type, representing a pinnacle of precision oncology.

Other names

Neoantigen-specific T-cell receptorMutation-specific T-cell receptorPersonalized TCRNeoTCRPatient-specific TCR

Adoptive transfer of T cells engineered to express a TCR that specifically binds to a patient-unique neoantigen-HLA complex, triggering direct tumor cell lysis.