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Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) protein family that plays a dual role in suppressing programmed cell death and regulating the cell cycle. While highly expressed during fetal development, it is nearly absent in normal adult tissues but significantly overexpressed in a wide range of human malignancies, including glioblastoma, melanoma, and breast cancer. The Sur1M2 epitope is a synthetic 9-mer peptide (LMLGEFLKL) derived from Survivin residues 96-104, modified with a leucine-to-methionine substitution at the second position to enhance its binding affinity to the HLA-A*02:01 MHC class I molecule. This peptide-MHC complex is presented on the surface of tumor cells, where it serves as a specific target for recognition by T-cell receptors (TCRs) on cytotoxic T-lymphocytes (CTLs). Therapeutic strategies targeting this complex, such as peptide vaccines and TCR-engineered T-cell therapies, aim to harness the immune system to selectively eliminate Survivin-positive cancer cells. However, potential safety concerns include on-target off-tumor effects due to low-level Survivin expression in certain normal proliferating cells, such as hematopoietic stem cells.
Induction of antigen-specific cytotoxic T-lymphocyte (CTL) response against Survivin-expressing tumor cells.
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