Survivin-derived peptide–Major Histocompatibility Complex (Survivin-MHC) (Survivin-MHC complex)

Survivin-derived peptide–Major Histocompatibility Complex (MHC) refers to the presentation of short peptide fragments derived from the survivin protein (BIRC5) on the surface of cells via MHC class I molecules, most commonly HLA-A*02:01 (UniProt P45883; PMID: 10833470). Survivin is a member of the inhibitor of apoptosis (IAP) family and is uniquely characterized by its high expression in nearly all human malignancies and its virtual absence in most terminally differentiated normal tissues (PMID: 15150571). This differential expression profile makes the survivin-MHC complex a highly attractive target for cancer immunotherapy, as it allows the immune system to distinguish between malignant and healthy cells. Therapeutic strategies targeting these complexes include peptide-based vaccines, such as SurVaxM, which stimulate the patient's own immune system to produce survivin-specific cytotoxic T lymphocytes (CTLs) (NCT02455557). Additionally, adoptive T-cell therapies using T-cell receptors (TCRs) are being engineered to recognize the specific peptide-MHC configuration directly (PMID: 21415215). By binding to these complexes, CTLs release perforins and granzymes to induce apoptosis in the target tumor cells. Clinical applications are being explored across a wide range of cancers, including glioblastoma and hematological malignancies, where survivin expression is often associated with poor prognosis and resistance to conventional therapies (PMID: 12853486). The specificity of the target is crucial for minimizing off-tumor toxicity, although low-level expression in certain normal stem cell populations remains a therapeutic challenge.

Other names

Survivin-HLA complexBIRC5 peptide-MHC complexSurvivin-derived peptide-HLA-A*0201pMHC complex (Survivin)

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis (PMID: 21415215).