T-cell receptor specific for glioma-associated antigen peptide–MHC complexes (GAA-specific TCR)

The T-cell receptor (TCR) specific for glioma-associated antigen (GAA) peptide–MHC complexes is a therapeutic receptor engineered into T cells to target malignant brain tumors (Frontiers in Immunology, 2021). These TCRs are designed to recognize specific peptides derived from proteins overexpressed in gliomas, such as Survivin, EphA2, or IL-13Rα2, or mutation-derived neoantigens like H3.3 K27M, when presented by Major Histocompatibility Complex (MHC) molecules (Nature Medicine, 2018; NIH). By targeting these peptide-MHC complexes, TCR-engineered T cells can identify and eliminate tumor cells that may not express high levels of surface antigens required for CAR-T cell recognition (Journal of Neuro-Oncology). The interaction between the TCR and the peptide-MHC complex initiates a robust immune response, including the release of cytotoxic molecules like granzymes and perforins, as well as pro-inflammatory cytokines (PubMed). This approach is particularly valuable in neuro-oncology due to the ability of TCRs to target intracellular antigens, which constitute the majority of the tumor proteome (Immatics.com). However, the success of these therapies depends on the presence of specific HLA alleles in patients and the ability of the T cells to penetrate the blood-brain barrier and overcome the immunosuppressive microenvironment of the glioma (StatPearls).

Other names

Glioma-specific T-cell receptorGlioma-associated antigen-specific TCRMHC-restricted glioma TCRTCR-T for glioma

MHC-restricted recognition of specific glioma-associated antigen peptides leading to T-cell activation, cytokine release, and direct tumor cell lysis (Nature Medicine, 2018).