T cell receptor recognizing hTERT- and Survivin-derived peptide–MHC complexes (hTERT/Survivin-specific TCR)

The T cell receptor (TCR) recognizing hTERT- and Survivin-derived peptide–MHC complexes is a specialized immune receptor used in adoptive T-cell therapies to target cancer cells. hTERT (human Telomerase Reverse Transcriptase) and Survivin (BIRC5) are considered universal tumor-associated antigens (TAAs) because they are overexpressed in over 85-90% of all human cancers, including multiple myeloma, leukemia, and various solid tumors, while being largely absent in healthy adult tissues. These TCRs are engineered or naturally identified to bind with high affinity to specific peptides from these proteins when presented by Major Histocompatibility Complex (MHC) molecules, such as HLA-A*02:01. Upon recognition of the peptide-MHC complex, the TCR triggers a signaling cascade that activates the T cell to release cytotoxic molecules like perforin and granzymes, leading to the selective destruction of the tumor cell. This dual-targeting strategy is employed to enhance therapeutic efficacy, overcome tumor heterogeneity, and prevent immune escape, though it faces challenges such as fratricide (where T cells kill each other due to low-level antigen expression) and potential off-tumor toxicities in tissues like bone marrow.

Other names

hTERT-specific T cell receptorSurvivin-specific T cell receptorTelomerase-specific TCRBIRC5-specific TCRhTERT/Survivin TCR-TRadium-4 TCRs24-TCR

The T cell receptor (TCR) specifically binds to peptide-MHC complexes (pMHC) on the surface of tumor cells, where the peptides are derived from hTERT or Survivin. This binding triggers T cell activation, leading to the release of cytotoxic granules (perforin, granzymes) and cytokines (IFN-gamma, TNF-alpha) that induce apoptosis in the target tumor cell.