Baculoviral IAP repeat-containing protein 5 (Survivin) peptide-HLA complex (Survivin-pMHC)

Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) protein family that regulates both cell death and the mitotic spindle checkpoint (UniProt: O15392). While Survivin is highly expressed during fetal development, it is nearly absent in adult tissues but becomes significantly overexpressed in most human cancers (PubMed: 12778136). Intracellular Survivin is degraded by the proteasome into peptides, which are then transported into the endoplasmic reticulum and loaded onto Human Leukocyte Antigen (HLA) Class I molecules. These Survivin-peptide-HLA complexes are presented on the cell surface, where they serve as specific targets for recognition by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (PubMed: 24743956). Therapeutic strategies targeting these complexes include peptide vaccines like SurVaxM and DPX-Survivac, which aim to elicit an endogenous immune response against tumor cells (PubMed: 30655270). Additionally, adoptive cell therapies using T-cells engineered with Survivin-specific TCRs are being developed to provide a more potent and direct anti-tumor effect (ClinicalTrials.gov: NCT02455557). Because Survivin is essential for tumor cell survival and proliferation, it is considered an ideal target with a low risk of immune escape through target downregulation (PubMed: 15187115).

Other names

BIRC5SurvivinAPI4Survivin-HLA complexSurvivin-MHC class I complexBaculoviral IAP repeat-containing 5

Induction of cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells through recognition of Survivin-derived peptides presented by HLA Class I molecules.