T cell receptor recognizing survivin peptide–MHC complexes (Survivin-specific TCR) (Survivin-specific TCR)

The T cell receptor (TCR) recognizing survivin peptide–MHC complexes is an engineered immune receptor designed to target the inhibitor of apoptosis protein (IAP) survivin (BIRC5). Survivin is highly expressed in the majority of human cancers, including lung, breast, and colon carcinomas, as well as hematologic malignancies, while being nearly undetectable in most normal adult tissues (Altieri, 2003, Nature Reviews Cancer). This differential expression makes the survivin peptide–MHC complex an attractive target for TCR-T cell therapy. The TCR is typically engineered to recognize a specific survivin-derived peptide, such as the HLA-A*02:01-restricted Sur9 (ELTLGEFLKL) epitope (Shraibman et al., 2018, Cancer Immunology Research). Upon binding to the peptide-MHC complex on the surface of a tumor cell, the TCR triggers T cell activation, leading to the release of cytotoxic granules and pro-inflammatory cytokines that mediate tumor cell lysis. Clinical trials are currently evaluating the safety and efficacy of T cells transduced with these TCRs in patients with various advanced malignancies (Fenstermacher et al., 2021, Frontiers in Immunology).

Other names

Survivin-specific T-cell receptorBIRC5-specific TCRAnti-survivin TCRSurvivin-restricted T-cell receptorHLA-A*02:01/Survivin-specific TCR

Engineered T cells expressing the TCR bind to survivin-derived peptides presented by MHC class I molecules on tumor cells, triggering T cell activation and targeted lysis of the malignant cells (Fenstermacher et al., 2021, Frontiers in Immunology).