Survivin-derived peptide–Major Histocompatibility Complex (Survivin-pMHC)

Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in nearly all human malignancies but is nearly undetectable in most normal adult tissues (UniProt: O15392). The Survivin-derived peptide–MHC complex is formed when intracellular Survivin is proteolytically processed by the proteasome and its peptide fragments are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (PubMed: 17634284). This cell-surface presentation allows the immune system to recognize an otherwise intracellular protein, making it a viable target for immunotherapies such as peptide vaccines and engineered T-cell receptor (TCR) therapies. Drugs like SurVaxM are designed to stimulate an endogenous immune response against these specific complexes to selectively eliminate tumor cells (PubMed: 27323818). Because Survivin is essential for tumor cell survival and resistance to apoptosis, targeting its pMHC complex provides a mechanism to bypass traditional drug resistance. Clinical development of therapies targeting this complex is ongoing in various high-grade malignancies, including glioblastoma and multiple myeloma (ClinicalTrials.gov: NCT02455557).

Other names

BIRC5-derived peptide-MHC complexSurvivin-HLA complexHLA-A*02:01/Survivin peptide complexSurvivin-MHC class I complexBaculoviral IAP repeat-containing protein 5-pMHC

Induction of cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells through the recognition of specific Survivin peptide fragments presented on MHC Class I molecules.