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

The T-cell receptor (TCR) recognizing patient-specific peptide-MHC complexes is a specialized immune receptor that serves as the cornerstone of personalized adoptive T-cell therapy (TCR-T). These receptors are either naturally occurring or genetically engineered to specifically bind to neoantigens—mutated peptides derived from a patient's unique tumor mutations—presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. By targeting these "private" neoantigens, the therapy achieves high tumor specificity and minimizes the risk of "on-target, off-tumor" toxicity, which occurs when the target antigen is also expressed in healthy tissues. The therapeutic process involves identifying neoantigens through genomic sequencing of the patient's tumor, followed by the isolation or design of TCRs with high affinity for these specific peptide-MHC complexes. These TCRs are then introduced into the patient's own T cells, which are expanded ex vivo and reinfused to mediate a targeted and potent anti-tumor immune response. This approach is particularly promising for treating solid tumors with high mutational burdens, such as melanoma and lung cancer, where it leverages the TCR's ability to recognize intracellular proteins. However, challenges remain, including the complexity of personalized manufacturing, the requirement for specific HLA matching, and the potential for tumor escape through HLA downregulation or antigen loss.

Other names

Neoantigen-specific T-cell receptorPersonalized T-cell receptorTumor-specific T-cell receptorNeoTCRPatient-specific TCR

Adoptive cell transfer of T cells engineered to express a neoantigen-specific T-cell receptor, which recognizes and binds to patient-specific peptide-MHC complexes on tumor cells, leading to T-cell activation and tumor cell lysis.