Survivin peptide–Major Histocompatibility Complex (Survivin pMHC)

Survivin (BIRC5) is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in nearly all human malignancies but has very limited expression in normal adult tissues. Peptides derived from the intracellular processing of survivin are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, specifically MHC Class I (e.g., HLA-A*02:01). These survivin peptide–MHC (pMHC) complexes serve as highly specific targets for immunotherapy, enabling the immune system to distinguish between cancerous and healthy cells. Therapeutic approaches include peptide vaccines like SurVaxM, which prime the immune system, and advanced modalities like TCR-engineered T-cells (TCR-T) and TCR-CD3 bispecific molecules (e.g., ABBV-184) that directly bind the pMHC complex. By targeting these complexes, therapies induce a potent cytotoxic T-lymphocyte (CTL) response that leads to the selective destruction of survivin-overexpressing tumor cells.

Other names

Baculoviral IAP repeat-containing protein 5 peptide–MHC complexBIRC5 peptide–MHC complexSurvivin–HLA-A*02:01 complexSurvivin epitope–MHC complexSurvivin peptide–HLA complex

Drugs targeting the survivin pMHC complex work by facilitating the recognition of tumor cells by the immune system. Vaccines like SurVaxM stimulate the production of endogenous survivin-specific CD8+ and CD4+ T cells, while TCR-engineered T-cells (TCR-T) and TCR-CD3 bispecific molecules (e.g., ABBV-184) directly bind the peptide–MHC complex on the tumor surface. This engagement triggers T-cell activation, the release of cytotoxic granules such as granzyme B and perforin, and the subsequent lysis of the survivin-expressing cancer cell.