Protein tyrosine phosphatase receptor type Z1-specific T-cell receptor (PTPRZ1-TCR)

The Protein tyrosine phosphatase receptor type Z1-specific T-cell receptor (PTPRZ1-TCR) is an engineered or patient-derived immune receptor designed to recognize specific peptides from the PTPRZ1 protein presented by Major Histocompatibility Complex (MHC) molecules (1.2.2, 1.2.5). PTPRZ1 is a highly relevant antigen in neuro-oncology, as it is significantly overexpressed in glioblastoma stem cells (GSCs), which are responsible for tumor initiation, radioresistance, and recurrence (1.2.1, 1.2.4). By targeting GSC-derived peptide-MHC complexes, specifically in the context of HLA-A*02:01, these TCRs allow T cells to selectively identify and eliminate the most aggressive subpopulations of glioblastoma (1.2.2, 1.2.3). This approach circumvents the limitations of traditional therapies that often fail to eradicate the stem cell niche. In therapeutic applications, such as TCR-engineered T-cell (TCR-T) therapy, these receptors are transduced into autologous T cells which are then re-infused into the patient (1.1.3, 1.2.5). Clinical trials, including the INVENT4GB study, are currently investigating the safety and efficacy of this approach, particularly focusing on overcoming the immunosuppressive environment of the central nervous system and ensuring precise targeting to minimize off-tumor effects (1.2.4, 1.2.5).

Other names

T-cell receptor recognizing GSC-derived peptide–MHC complexesPTPRZ1-reactive T-cell receptorGlioblastoma stem cell-specific T-cell receptorPTPRZ1-specific TCR

Recognition of PTPRZ1-derived peptide-MHC complexes (specifically HLA-A*02:01) on the surface of glioma stem cells, triggering T-cell activation and selective lysis of the tumor cells.