Neoantigen-specific T cell receptor complex (NeoTCR)

Neoantigen-specific T cell receptor (TCR) complexes are specialized protein assemblies found on the surface of CD8+ and CD4+ T cells that recognize unique, mutation-derived peptides (neoantigens) presented by Major Histocompatibility Complex (MHC) molecules. Unlike traditional TCRs that may target shared self-antigens, neoantigen-specific TCRs are highly selective for tumor-specific mutations, minimizing the risk of attacking healthy tissues. These complexes consist of a polymorphic alpha-beta heterodimer that determines antigen specificity, non-covalently associated with CD3 signaling subunits (Source: PubMed PMID: 31142863). In therapeutic applications, such as TCR-T cell therapy, these receptors are identified from a patient's own tumor-infiltrating lymphocytes or generated via synthetic libraries and then expressed in peripheral T cells to create a personalized immunotherapy. This approach is particularly promising for treating solid tumors with high mutational burdens, as it leverages the immune system's ability to detect subtle genetic alterations unique to the malignancy (Source: Science, DOI: 10.1126/science.aba7365).

Other names

Neoantigen-reactive T-cell receptorMutation-specific T-cell receptorTumor-specific TCRNeoepitope-specific TCRPersonalized T-cell receptor

Neoantigen-specific T cell receptors are engineered into a patient's T cells (TCR-T therapy) to recognize and bind specific neoepitopes presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells. Upon binding, the TCR complex initiates intracellular signaling through the CD3 subunits, leading to T cell activation, proliferation, and the release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines (IFN-gamma, TNF-alpha) to eliminate the target tumor cells (Source: PubMed PMID: 33024314, Nature Reviews Cancer).