Survivin-derived peptide-MHC class I complex (Survivin-pMHC)

Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) protein family that plays a dual role in suppressing programmed cell death and regulating cell division (Altieri, 2008). While survivin is highly expressed during fetal development, it is nearly undetectable in most normal adult tissues but is prominently overexpressed in a wide range of cancers, including glioblastoma and ovarian cancer (Wheatley & Altieri, 2019). This differential expression makes survivin-derived peptides, when processed and presented by MHC Class I molecules on the cell surface, ideal tumor-associated antigens (TAAs) for immunotherapy (Andersen et al., 2001). The survivin-derived peptide-MHC class I complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which can be leveraged for therapeutic intervention (Fenstermaker et al., 2022). Current strategies targeting this complex include peptide-based vaccines like SurVaxM and DPX-Survivac, which aim to prime the patient's own immune system to recognize the epitope (Ahluwalia et al., 2023). Additionally, advanced modalities such as TCR-engineered T-cells (TCR-T) and TCR-like antibodies are being developed to directly bind this specific pMHC configuration with high affinity. Targeting this complex provides a mechanism to induce apoptosis and immune-mediated lysis specifically in malignant cells while minimizing damage to healthy tissue.

Other names

BIRC5 peptide-MHC complexSurvivin-HLA complexSurvivin-derived epitopeSurvivin-MHC-ISurvivin-HLA-A*02:01 complex

Induction of cytotoxic T-lymphocyte (CTL) response through T-cell receptor (TCR) binding to the peptide-MHC complex, leading to selective lysis of tumor cells.