Human epidermal growth factor receptor 2-specific MHC Class II-restricted T cell receptor (HER2-specific CD4+ TCR)

The Human epidermal growth factor receptor 2-specific MHC Class II-restricted T cell receptor is an engineered or naturally occurring immune receptor that recognizes HER2-derived peptides presented by Major Histocompatibility Complex (MHC) Class II molecules (Wang et al., 2018, Journal of Immunology). While HER2 is a well-known oncogene overexpressed in breast and gastric cancers, this specific TCR targets the CD4+ T cell pathway, which is essential for coordinating long-term anti-tumor immunity and enhancing the activity of CD8+ T cells (Perez-Diez et al., 2007, Blood). Upon binding to the HER2/MHC II complex, the TCR triggers T cell activation and the secretion of pro-inflammatory cytokines such as interferon-gamma and TNF-alpha (Borbulevych et al., 2010, Journal of Molecular Biology). This target is currently being explored in adoptive cell transfer therapies, where patient T cells are engineered to express the TCR to specifically attack HER2-positive tumor cells (NCI, ClinicalTrials.gov). However, a major therapeutic challenge is the potential for on-target, off-tumor toxicity, particularly cardiotoxicity, due to low-level HER2 expression in normal cardiac tissue (Slamon et al., 2001, New England Journal of Medicine). Additionally, the efficacy of this target is restricted by the patient's HLA haplotype, requiring precise MHC matching for successful treatment (Stevanović et al., 2017, Science).

Other names

HER2-specific TCRERBB2-specific T cell receptorMHC II-restricted HER2 TCRCD4+ HER2 TCR

Recognition of HER2-derived peptides presented by MHC Class II molecules, leading to CD4+ T cell activation and orchestration of an anti-tumor immune response.