Baculoviral IAP repeat-containing protein 5 (BIRC5) HLA-A2-restricted peptide (Survivin/HLA-A2 epitope)

Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) family that plays a dual role in suppressing programmed cell death and regulating cell division (UniProt: O15392). It is highly overexpressed in nearly all human malignancies but is largely undetectable in most normal adult tissues, making it a prominent tumor-associated antigen (TAA) (PubMed: 11160652). HLA-A2-restricted epitopes are specific short peptide sequences derived from the survivin protein that are processed and presented on the cell surface by the Human Leukocyte Antigen A2 (HLA-A2) molecule. These peptide-MHC complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune-mediated attack against the cancer cells (PubMed: 12738670). Therapeutic approaches leveraging these epitopes include peptide-based vaccines, such as SurVaxM, and adoptive cell therapies designed to overcome immune tolerance and eradicate survivin-positive tumors (PubMed: 24743956). Clinical trials have demonstrated that targeting these epitopes can induce robust immune responses with a favorable safety profile across various solid and hematological cancers (PubMed: 21415217). Because survivin is essential for cancer cell survival, it is difficult for tumors to downregulate its expression without compromising their own viability, potentially reducing the risk of antigen-loss escape. However, the effectiveness of these therapies is limited to patients carrying the HLA-A2 allele, necessitating genetic screening prior to treatment.

Other names

Survivin-derived HLA-A2-restricted epitopesBIRC5 epitopesHLA-A*0201-restricted survivin peptidesSurvivin-derived peptidesSurvivin-A2 epitopesSurVaxM target

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) responses against tumor cells presenting survivin peptides on HLA-A2 molecules (PubMed: 11160652).