HER2-specific T-cell receptor (HER2-TCR)

The HER2-specific T-cell receptor (TCR) is a specialized protein complex found on the surface of engineered or naturally occurring CD4+ and CD8+ T cells that specifically recognizes peptides derived from the Human Epidermal Growth Factor Receptor 2 (HER2) protein presented by Major Histocompatibility Complex (MHC) molecules (PubMed: 20168310). Unlike Chimeric Antigen Receptors (CARs) which recognize surface proteins, these TCRs can detect intracellularly processed HER2 fragments, expanding the range of targetable epitopes (PubMed: 31515461). In the context of oncology, HER2 is frequently overexpressed in various malignancies, including breast, gastric, and lung cancers, making it a primary target for immunotherapy (PubMed: 28103468). When the TCR binds to the HER2 peptide-MHC complex, it triggers a signaling cascade that leads to T-cell activation, proliferation, and the targeted destruction of the cancer cell. Therapeutic strategies involving these receptors primarily focus on TCR-engineered T-cell (TCR-T) therapies, where a patient's T cells are modified to express a high-affinity HER2-specific TCR (ClinicalTrials.gov: NCT03939234). However, safety remains a critical concern, as low-level HER2 expression in healthy tissues, such as the heart and lungs, can lead to severe on-target, off-tumor toxicities (PubMed: 20168310). Monitoring for cytokine release syndrome and neurotoxicity is also essential during treatment with these engineered cells. The specificity of the TCR for particular HLA alleles, such as HLA-A*02:01, necessitates patient screening to ensure compatibility with the therapeutic TCR (PubMed: 25103341).

Other names

HER2-specific TCRErbB2-specific T-cell receptorHER2/neu-specific T-cell receptorHER2 peptide-MHC specific TCR

Recognition of HER2-derived peptides presented by MHC molecules, leading to T-cell activation and lysis of HER2-expressing tumor cells.