Lymphocyte antigen 6 family member E-specific T-cell receptor (LY6E-specific TCR)

LY6E-specific T-cell receptors (TCRs) are engineered or naturally occurring immune receptors designed to recognize peptides derived from the Lymphocyte Antigen 6 Family Member E (LY6E) protein when presented by Major Histocompatibility Complex (MHC) molecules. LY6E is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that is significantly overexpressed in various solid malignancies, including breast, lung, gastric, and ovarian cancers, where it is associated with poor prognosis and immune evasion. These TCRs are primarily utilized in adoptive T-cell therapy (TCR-T), where a patient's T cells are genetically modified to express the receptor to selectively identify and eliminate LY6E-positive tumor cells. Beyond its role as a tumor-associated antigen, LY6E is involved in regulating T-cell physiology and facilitating the entry of several viruses, including SARS-CoV-2 and HIV. Therapeutic development targeting LY6E includes TCR-T cells, antibody-drug conjugates (ADCs), and multispecific T-cell engagers. However, potential safety concerns include off-tumor toxicity due to low-level LY6E expression in certain healthy tissues such as the liver, lungs, and normal T cells.

Other names

LY6E-targeted TCRTCRs specific for LY6ETSA-1-specific TCRSCA-2-specific TCRRIG-E-specific TCR

Engineered T-cell receptors recognize LY6E-derived peptides presented by MHC molecules (typically HLA-A*02:01) on the surface of tumor cells, triggering T-cell activation, cytokine secretion (e.g., IFN-gamma), and direct cytotoxic killing of the target cell via perforin and granzymes.