Survivin-derived peptide-HLA-A*02:01 complex (Survivin-HLA-A2) (Survivin-HLA-A2)

The survivin-derived peptide-HLA-A*02:01 complex is a tumor-associated antigen (TAA) that serves as a critical target for cancer immunotherapy. Survivin, encoded by the BIRC5 gene, is an inhibitor of apoptosis (IAP) protein that is highly expressed in nearly all human malignancies but is largely absent in terminally differentiated normal adult tissues (Altieri, 2003). Intracellular survivin is proteolytically processed into short peptides, such as the immunodominant HLA-A*02:01-restricted decamer ELTLGEFLKL (survivin 95-104), which are then loaded onto MHC class I molecules and presented on the cell surface (Schmitz et al., 2000). This peptide-MHC (pMHC) complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a focal point for therapeutic strategies including peptide-based vaccines like SurVaxM and adoptive T-cell therapies using TCR-engineered T cells (Fenstermaker et al., 2016). Targeting this complex allows for the selective destruction of tumor cells that rely on survivin for anti-apoptotic signaling and mitotic progression. However, clinical application is restricted to patients carrying the HLA-A*02:01 allele, and potential safety concerns regarding off-target effects on survivin-expressing healthy cells, such as hematopoietic progenitors or vascular endothelium, remain a consideration (Pisarev et al., 2003).

Other names

Survivin-HLA-A*02:01 complexBIRC5-HLA-A2 complexSurvivin peptide-MHC complexHLA-A2/Survivin(95-104)HLA-A2/Survivin(96-104)

Induction of CD8+ T-cell mediated cytotoxicity through the specific recognition of survivin peptides presented by HLA-A*02:01 on the tumor cell surface, leading to granzyme-mediated apoptosis of the target cell (Schmitz et al., 2000).