HLA-A*02:01-restricted tumor-associated antigen peptides (p53, Survivin, hTERT) (HLA-A2/TAA peptides)

The target consists of specific peptide fragments derived from the intracellular proteins p53, survivin (BIRC5), and human telomerase reverse transcriptase (hTERT), which are presented on the cell surface by the Human Leukocyte Antigen A2 (HLA-A*02:01) molecule (UniProt P01892, P04637, O15392, O14746). These proteins are prominent tumor-associated antigens (TAAs) that are frequently overexpressed or mutated in a wide range of malignancies, including lung, breast, and colorectal cancers, while remaining largely absent or restricted in normal adult tissues (PubMed 15150595, 11156400). Because these proteins are located within the cell, they are inaccessible to standard antibody therapies; however, their degradation and subsequent presentation as peptide-MHC complexes allow them to be recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes (PubMed 10491260). Therapeutic interventions targeting these HLA-A2-restricted complexes include multi-peptide vaccines like UV1 and DPX-Survivac, TCR-engineered T-cell therapies (TCR-T), and TCR-mimetic antibodies (NCT03538314, NCT03834974). These strategies aim to overcome immune tolerance and stimulate a robust, multi-antigenic immune response to prevent tumor escape, which often occurs when only a single antigen is targeted. Clinical applications primarily focus on HLA-A2-positive patients, utilizing these complexes as precise markers for directing the immune system to identify and destroy cancerous cells while minimizing damage to healthy tissues.

Other names

HLA-A2-restricted p53/Survivin/hTERT peptidespMHC complexesTumor-associated antigen peptide-HLA complexesHLA-A*02:01/p53-Survivin-hTERTMHC Class I-restricted tumor antigens

Recognition of peptide-MHC complexes by T-cell receptors (TCRs) or TCR-mimetic molecules to induce T-cell mediated cytotoxicity against tumor cells.