T cell receptor recognizing IMA950 peptide–HLA-A2 complexes (IMA950-TCR)

The T cell receptor (TCR) recognizing IMA950 peptide–HLA-A2 complexes is a specialized immune receptor that mediates the recognition of glioblastoma cells by the adaptive immune system. IMA950 is a therapeutic vaccine composed of 11 tumor-associated peptides (TUMAPs), nine of which are restricted to the HLA-A*02:01 allele, identified directly from the peptidome of primary glioblastoma tissues (Dutoit et al., 2012). These TCRs are designed or naturally induced to bind with high specificity to these peptide-MHC complexes, which include antigens derived from proteins like PTPRZ1, MET, and brevican that are overexpressed in gliomas (Rampling et al., 2016). Upon binding, the TCR triggers a signaling cascade that leads to the activation and cytotoxic activity of CD8+ T cells against the tumor. Therapeutic development centered on these TCRs includes the IMA950 vaccine, which aims to stimulate the patient's endogenous T-cell repertoire, and experimental adoptive cell therapies using TCR-engineered T cells (Immatics, 2024). Clinical studies have explored the use of IMA950 in combination with adjuvants such as poly-ICLC and immune checkpoint inhibitors like pembrolizumab to overcome the immunosuppressive environment of the central nervous system (Migliorini et al., 2019). The primary goal of targeting these TCR-peptide-HLA interactions is to provide a precise, long-lasting anti-tumor response with minimal off-target effects on healthy brain tissue.

Other names

IMA950-specific T-cell receptorGlioblastoma-associated antigen-specific TCRTCR recognizing glioblastoma TUMAPsT-cell receptor recognizing glioma-associated peptide-HLA complexes

The TCR specifically recognizes and binds to tumor-associated peptides (TUMAPs) from the IMA950 vaccine presented by HLA-A*02:01 molecules on glioblastoma cells, triggering T-cell activation, proliferation, and targeted lysis of the tumor cells.