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

Survivin-derived peptide–MHC class I complexes are specialized molecular structures presented on the surface of tumor cells, consisting of short peptide fragments from the Survivin protein (BIRC5) bound within the groove of Major Histocompatibility Complex (MHC) class I molecules (Altieri, D. C., 2003, Nature Reviews Cancer). Survivin is a prominent member of the inhibitor of apoptosis (IAP) protein family and plays a dual role in suppressing programmed cell death and regulating mitosis (Widenmeyer, M., et al., 2012, Cancer Immunology, Immunotherapy). While Survivin is highly expressed during fetal development and in the vast majority of human cancers, its expression is minimal or absent in most healthy adult tissues, making these complexes highly specific tumor-associated antigens (TAAs) (Shraibman, B., et al., 2018, Cancer Immunology Research). In the context of immunotherapy, these complexes are targeted to trigger a cytotoxic T-lymphocyte (CTL) response against malignant cells. Current therapeutic strategies include peptide-based vaccines like SurVaxM, which stimulate the patient's own immune system to recognize these complexes, and adoptive T-cell therapies using T-cell receptors (TCRs) engineered to bind specifically to the Survivin-peptide-HLA interface (Fenstermaker, R. A., et al., 2016, Cancer Immunology, Immunotherapy). By targeting the peptide-MHC complex, these therapies bypass the need for the target protein to be on the cell surface in its native form, allowing the immune system to attack intracellular oncogenic drivers.

Other names

Survivin-peptide-HLA complexBIRC5-derived peptide-MHC complexSurvivin-pMHCSurvivin-HLA-A*02:01 complexSurvivin-derived peptide-HLA complex

Targeting of tumor cells via T-cell receptor (TCR) recognition of specific peptide-MHC complexes, leading to T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and direct lysis of the malignant cell.