T cell receptor recognizing Mucin 1 (MUC1) and Wilms Tumor 1 (WT1) peptide–HLA complexes (TCR (MUC1/WT1))

T cell receptors (TCRs) recognizing Mucin 1 (MUC1) and Wilms Tumor 1 (WT1) peptide–HLA complexes are engineered immune receptors used in adoptive cell therapy to target specific tumor-associated antigens. MUC1 is a heavily glycosylated protein overexpressed in various adenocarcinomas, including breast, lung, and pancreatic cancers, where it contributes to oncogenic signaling and immune evasion [UniProt: P15941]. WT1 is a zinc-finger transcription factor that is highly expressed in acute myeloid leukemia (AML) and several solid tumors, serving as a marker of minimal residual disease and a driver of malignancy [UniProt: P19544]. These TCRs are designed to recognize specific peptide fragments of MUC1 or WT1 when presented by Human Leukocyte Antigen (HLA) molecules, most commonly the HLA-A*02:01 allele [PubMed: 30249024]. Therapeutically, these TCRs are introduced into a patient's T cells via viral vectors to create TCR-engineered T (TCR-T) cells. Upon infusion, these cells recognize the peptide-HLA complexes on tumor surfaces, leading to T-cell activation, the release of cytotoxic molecules like perforin and granzymes, and the production of pro-inflammatory cytokines such as interferon-gamma [PubMed: 27141018]. This approach allows for the targeting of intracellular antigens like WT1, which are inaccessible to standard CAR-T cell therapies. Clinical development of these TCR-Ts, such as TBI-1501 for WT1, aims to provide a precise immunotherapy option while managing risks like on-target off-tumor toxicity and cytokine release syndrome [ClinicalTrials.gov: NCT01621490].

Other names

MUC1-specific T-cell receptorWT1-specific T-cell receptorMUC1/WT1-targeted TCRTCR-T targeting MUC1 and WT1Anti-MUC1 TCRAnti-WT1 TCR

TCR-engineered T cells recognize specific peptide-HLA complexes on the surface of tumor cells. This recognition triggers the CD3 signaling cascade, leading to the formation of an immunological synapse and the subsequent release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines (IFN-gamma, TNF-alpha), which induce apoptosis and lysis of the target cell [PubMed: 27141018].