Major histocompatibility complex presenting Survivin-derived peptides (MHC-Survivin) (MHC-Survivin)

Survivin (BIRC5) is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in most human cancers but largely absent in normal differentiated tissues (UniProt P50281). The presentation of Survivin-derived peptides by the Major Histocompatibility Complex (MHC), particularly HLA-A*02:01, creates a unique cell-surface target for immunotherapy (Andersen et al., 2001, Cancer Res). This complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, which can then eliminate the tumor cells. Therapeutic strategies include peptide vaccines like SurVaxM designed to elicit an endogenous immune response and engineered TCR-T cells that directly bind the MHC-peptide complex (Fenstermaker et al., 2016, Cancer Immunol Immunother). Because Survivin is essential for tumor cell survival and mitosis, it is considered an ideal tumor-associated antigen with a low risk of antigen loss (Wheatley & Altieri, 2019, Nat Rev Cancer). The complex serves as a bridge between the intracellular proteome and the immune system, allowing for the targeting of an intracellular protein that would otherwise be inaccessible to traditional antibody therapies. Clinical trials have demonstrated that targeting this complex can induce robust T-cell responses and improve survival in patients with glioblastoma and other solid tumors. The specificity of the interaction depends on both the Survivin peptide sequence and the specific MHC allele, making patient HLA typing a critical component of therapy.

Other names

HLA-Survivin complexBIRC5-MHC complexSurvivin-HLA-A*02:01 complexSurvivin-MHC class I complexpMHC-Survivin

Induction of cytotoxic T lymphocyte (CTL) responses against cells presenting Survivin-derived peptides on MHC class I molecules, leading to targeted cell lysis.