Patient-specific T-cell receptor (TCR) (TCR)

Patient-specific T-cell receptors (TCRs) are highly specialized heterodimeric surface proteins, typically consisting of alpha (α) and beta (β) chains, that play a fundamental role in the adaptive immune system by recognizing peptide antigens presented by major histocompatibility complex (MHC) molecules (Wikipedia, 2024). In the context of personalized oncology, these receptors are either isolated from a patient's own tumor-infiltrating lymphocytes (TILs) or genetically engineered to target unique, patient-specific neoantigens that arise from somatic mutations within the tumor (NIH, 2023). This individualized approach allows for the creation of TCR-engineered T-cell (TCR-T) therapies that can precisely identify and eliminate cancer cells while sparing healthy tissue (AACR, 2023). Beyond their role as a therapeutic modality, patient-specific TCRs can also serve as direct targets in the treatment of clonal T-cell malignancies, such as T-cell lymphomas, where the unique variable region (Vβ) of the malignant TCR is targeted by monoclonal antibodies to induce cell death (NIH, 2023). Therapeutic strategies utilizing these receptors include adoptive cell transfer and the development of TCR-mimic antibodies or bispecific engagers (tcrtcell.com, 2024). However, the clinical application of TCR-based therapies faces significant challenges, including the risk of cytokine release syndrome (CRS), neurotoxicity, and potential on-target off-tumor cross-reactivity with similar peptides in normal tissues (AACR, 2017).

Other names

Neoantigen-specific T-cell receptorPersonalized T-cell receptorTumor-reactive T-cell receptorClonal T-cell receptorT-cell antigen receptor

Adoptive cell transfer of TCR-engineered T cells to recognize specific pMHC complexes; antibody-mediated targeting of specific TCR variable regions to induce ADCC or activation-induced cell death.