T-cell receptor specific for programmed cell death 1 ligand 1-derived peptide-HLA complex (PD-L1-specific TCR) (PD-L1-specific TCR)

T-cell receptors (TCRs) specific for PD-L1-derived peptide-HLA complexes are specialized immune receptors engineered to recognize PD-L1 as a tumor-associated antigen (Munir et al., 2013, Leukemia). While PD-L1 is primarily known as an immune checkpoint ligand that suppresses T-cell activity, it is overexpressed in many cancers and its degradation products can be presented on the cell surface via HLA molecules (Ahmad et al., 2014, Oncoimmunology). These TCRs allow T cells to specifically target and kill PD-L1-expressing tumor cells and immunosuppressive cells, such as myeloid-derived suppressor cells, within the tumor microenvironment (Medigene AG, 2024). This approach effectively turns a mechanism of immune evasion into a target for immune destruction. Clinical candidates like MDG1015 utilize high-affinity TCRs to enhance the anti-tumor response in solid tumors (Medigene AG, 2024). However, because PD-L1 is also expressed at lower levels on some healthy tissues, a primary safety concern is on-target, off-tumor toxicity (NCI, 2023). The efficacy of these TCRs is often restricted by the patient's HLA type, most commonly HLA-A*02:01 (Ahmad et al., 2014).

Other names

PD-L1-targeted T-cell receptorTCR specific for PD-L1/HLA complexAnti-PD-L1 TCRPD-L1-specific TCR

The TCR recognizes and binds to specific PD-L1-derived peptides presented by HLA class I molecules (typically HLA-A*02:01) on the surface of target cells. This binding event triggers a signaling cascade through the CD3 complex, leading to T-cell activation, secretion of pro-inflammatory cytokines, and the release of cytotoxic granules (perforin and granzymes) to induce apoptosis in the PD-L1-expressing cell (Munir et al., 2013; Medigene AG, 2024).