Human leukocyte antigen class I-Survivin peptide complex (HLA-I/Survivin)

The Human leukocyte antigen (HLA) class I-Survivin peptide complex is a tumor-associated antigen (TAA) consisting of fragments of the Survivin protein (BIRC5) presented on the cell surface by HLA class I molecules (UniProt P50281). Survivin is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in the majority of human cancers but is nearly undetectable in most terminally differentiated normal tissues, making this complex a highly specific target for immunotherapy (Altieri, 2003, Nature Reviews Cancer). In cancer cells, Survivin is processed by the proteasome into short peptides, which are then transported into the endoplasmic reticulum and loaded onto HLA class I molecules for presentation to the immune system (PubMed 11160592). This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which can trigger the lysis of the presenting tumor cell (PubMed 15150570). Therapeutic strategies targeting this complex include peptide-based vaccines like SurVaxM, designed to elicit a robust anti-tumor T-cell response, and adoptive cell therapies using TCR-engineered T cells (Ahluwalia et al., 2023, Journal of Clinical Oncology). Because Survivin expression is often associated with resistance to chemotherapy and poor prognosis, targeting the HLA-Survivin complex offers a way to eliminate the most aggressive and treatment-resistant cell populations within a tumor. Successful targeting of this complex requires both the presence of the specific HLA allele in the patient and the overexpression of the BIRC5 gene in the tumor tissue.

Other names

HLA-A*02:01/Survivin complexBIRC5 peptide-MHC complexSurvivin-HLA complexpMHC SurvivinSurvivin-derived peptide-HLA class I complex

Drugs targeting this complex function by facilitating the recognition of tumor cells by the cellular immune system. Peptide vaccines stimulate the expansion of endogenous CD8+ T cells that recognize the Survivin peptide presented by HLA, while TCR-T therapies provide patients with pre-engineered T cells that bind specifically to this pMHC complex, leading to targeted cytotoxicity and tumor cell death.