Human leukocyte antigen A2 presenting tumor protein p53-derived peptide epitopes (HLA-A2-p53)

The Human leukocyte antigen A2 presenting tumor protein p53-derived peptide epitopes complex is a major target for cancer immunotherapy, facilitating the recognition of intracellular tumor-associated antigens by the adaptive immune system (Hsiue et al., 2021). HLA-A2, specifically the HLA-A*02:01 allele, is a highly prevalent MHC Class I molecule that presents short peptide fragments on the cell surface for CD8+ T-cell surveillance (Gonzalez-Galarza et al., 2020). These fragments include peptides derived from the tumor protein p53, which is mutated or overexpressed in over 50% of human cancers (Vogelstein et al., 2000). Because p53 mutations are often driver mutations, these peptide-MHC complexes serve as highly specific markers for malignant cells. Therapeutic interventions such as TCR-engineered T cells and bispecific T-cell engagers are designed to bind this complex with high affinity and specificity (Hsiue et al., 2021). These treatments aim to redirect the immune system to selectively destroy tumor cells while minimizing damage to healthy tissues. However, the clinical application of these therapies must address challenges such as potential cross-reactivity with wild-type p53 in normal tissues. Additionally, tumors may evade detection by downregulating HLA expression or through other immune escape mechanisms (Garrido et al., 2016). Despite these hurdles, targeting the p53/HLA-A2 complex remains a promising strategy for treating a wide range of solid tumors (NCT04350606).

Other names

HLA-A*02:01-p53 complexp53-MHC complexp53/HLA-A2 complexp53 peptide-HLA-A2 complexHLA-A2-p53

T-cell redirection and activation through specific recognition of the peptide-MHC complex, leading to the release of cytotoxic molecules and subsequent lysis of the target tumor cell.