Thyroglobulin-derived peptide-MHC complex (TG-pMHC)

The thyroglobulin-derived peptide-MHC complex is a tumor-associated antigen (TAA) target utilized in the development of T-cell receptor-engineered T-cell (TCR-T) therapies for thyroid cancer. Thyroglobulin (TG) is a large glycoprotein produced exclusively by thyroid follicular cells, where it serves as the essential precursor for thyroid hormone synthesis [1, 17]. In differentiated thyroid cancers, such as papillary and follicular thyroid carcinoma, TG is often overexpressed, and its intracellularly processed peptides are presented on the cell surface via Major Histocompatibility Complex (MHC) molecules, most notably HLA-A*02:01 [7, 21]. This peptide-MHC (pMHC) complex provides a specific molecular signature that allows engineered T cells to distinguish malignant thyroid cells from other non-thyroid tissues [10, 18]. While this approach offers a potential treatment for advanced or radioactive iodine-refractory thyroid cancer, it carries a significant risk of on-target, off-tumor toxicity because TG is also expressed in normal thyroid tissue [7, 14]. Consequently, successful treatment often results in the destruction of the healthy thyroid gland, leading to permanent hypothyroidism and requiring lifelong hormone replacement therapy [7, 11].

Other names

Thyroglobulin peptide-HLA complexTG-derived peptide-HLA-A*02:01 complexThyroglobulin-derived epitope-MHC complexTG-pMHC complex

Engineered T-cell receptors (TCRs) on adoptive T cells specifically bind to thyroglobulin-derived peptides presented by MHC molecules (typically HLA-A*02:01) on the surface of thyroid cancer cells, leading to T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and tumor cell lysis [7, 10, 18].