Survivin-derived peptide–MHC complex (Survivin-pMHC)

The Survivin-derived peptide–MHC complex is a tumor-associated antigen (TAA) complex formed by the presentation of survivin-derived peptides on the surface of cancer cells via Major Histocompatibility Complex (MHC) molecules [PubMed: 15150571]. Survivin (BIRC5) is a member of the inhibitor of apoptosis (IAP) family that is highly overexpressed in nearly all human malignancies but is largely absent in normal adult tissues, providing a wide therapeutic window for immunotherapy [UniProt: O15392]. This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which triggers an immune-mediated destruction of the tumor cell [PubMed: 25611625]. Because survivin is essential for both cell cycle progression and the inhibition of programmed cell death, it is considered a resistance-proof target, as tumor cells cannot easily downregulate its expression without compromising their own viability [PubMed: 12778136]. Current therapeutic approaches targeting this complex include peptide vaccines like SurVaxM and DPX-Survivac, as well as adoptive cell therapies using TCR-engineered T cells [ClinicalTrials.gov: NCT02455557]. These strategies aim to overcome the immunosuppressive tumor microenvironment by inducing a robust, peptide-specific cytotoxic T-cell response.

Other names

Survivin-HLA complexBIRC5 peptide-MHC complexHLA-presented survivin peptideSurvivin-derived peptide-HLA-A2 complexSurvivin-pMHC complex

Recognition by T-cell receptors (TCRs) on cytotoxic T lymphocytes (CTLs) leads to the targeted lysis of survivin-expressing tumor cells through the release of cytotoxic granules [PubMed: 25611625].