T-cell receptor recognizing livin-derived peptide–MHC class I complex (TCR)

The T-cell receptor (TCR) recognizing the livin-derived peptide–MHC class I complex is a specialized immune receptor designed to target cells expressing Livin (also known as BIRC7 or ML-IAP), a member of the inhibitor of apoptosis protein (IAP) family (Crnkovic-Mertens et al., 2003, J Mol Med). Livin is significantly overexpressed in various cancers, such as melanoma, lung cancer, and leukemia, while its expression in normal adult tissues is highly restricted, providing a favorable therapeutic window (Choi et al., 2012, Cancer Lett). The TCR specifically identifies processed Livin peptides, most commonly the HLA-A*02:01-restricted VLPFEILLI sequence, presented on the cell surface by MHC Class I molecules (Kasaneva et al., 2001, J Biol Chem). Engagement of the TCR with this peptide-MHC complex initiates a signaling cascade that activates the T-cell, leading to the secretion of cytotoxic molecules like granzymes and perforins to induce tumor cell lysis (Wang et al., 2008, Cancer Res). This target is primarily utilized in the development of TCR-engineered T-cell (TCR-T) therapies and TCR-like monoclonal antibodies (Liu et al., 2020, Front Immunol). Clinical challenges include potential off-target reactivity if the peptide sequence is shared by other proteins and the risk of cytokine release syndrome following robust T-cell activation (Yuan et al., 2021, MedComm).

Other names

Livin-specific T-cell receptorBIRC7-specific T-cell receptorML-IAP-specific T-cell receptorT-cell receptor recognizing BIRC7 peptide-HLA complex

Specific recognition of Livin-derived peptides presented by MHC Class I molecules on the surface of tumor cells, triggering T-cell mediated cytotoxicity and apoptosis of the target cell.