T cell receptor recognizing patient-specific neoantigen peptide–MHC complex (TCR-neoantigen-pMHC)

The T cell receptor (TCR) recognizing patient-specific neoantigen peptide–MHC (pMHC) complexes is a pivotal target in personalized adoptive cell therapy. Neoantigens are tumor-specific proteins arising from non-synonymous mutations, which are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Nature, 2017). Because these antigens are absent in healthy tissues, TCRs targeting them offer a high degree of specificity, minimizing the risk of systemic toxicity (Science, 2019). Therapeutic strategies involve identifying these unique mutations via whole-exome sequencing and engineering autologous T cells to express the corresponding TCR (Journal of Clinical Investigation, 2021). Once infused back into the patient, these TCR-engineered T cells bind to the pMHC complex, triggering a cytotoxic response that includes the release of perforin and granzymes to induce apoptosis in cancer cells (Frontiers in Immunology, 2020). This approach is particularly promising for treating solid tumors that have traditionally been resistant to other forms of immunotherapy. However, the success of this therapy depends on the accurate identification of immunogenic neoantigens and the stability of MHC expression on tumor cells. Ongoing clinical trials are evaluating the efficacy of these personalized TCR-T therapies across various epithelial and hematological malignancies.

Other names

Neoantigen-specific T cell receptorPersonalized TCRTumor-specific TCRNeo-TCRNeoantigen-reactive T cell receptor

The mechanism involves the recognition of a unique, patient-specific neoantigen peptide presented by the Major Histocompatibility Complex (MHC) by an engineered T cell receptor (TCR), which triggers T cell activation, expansion, and the targeted destruction of tumor cells through the release of cytotoxic molecules like granzymes and perforins (Nature Reviews Drug Discovery, 2021).