Cytotoxic T-lymphocyte T cell receptor recognizing HLA-A*2402–survivin-2B80-88 complex (HLA-A*2402–survivin-2B80-88 TCR)

The Cytotoxic T-lymphocyte T cell receptor (TCR) recognizing the HLA-A*2402–survivin-2B80-88 complex is a specialized immune recognition molecule that targets a specific epitope of the survivin-2B protein. Survivin-2B is a splice variant of survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) family that is highly expressed in many cancers but nearly undetectable in normal adult tissues (Clin Cancer Res. 2002;8(6):1731-9). The specific nonamer peptide, AYACNTSTL (residues 80-88), is presented on the cell surface by the human leukocyte antigen (HLA)-A*2402 molecule, which is particularly prevalent in Asian populations (J Transl Med. 2009;7:1). This TCR-pMHC (peptide-MHC) interaction is the basis for several immunotherapeutic strategies, including peptide vaccines often combined with adjuvants like interferon-alpha or interferon-beta (STI-01), TCR-engineered T cell (TCR-T) therapies, and TCR-mimic (TCRm) antibodies such as clone #21-3 (Sci Rep. 2019;9(1):9827). These therapies aim to harness the specificity of the TCR to direct a potent cytotoxic immune response against tumor cells. Clinical studies in patients with pancreatic, colorectal, and oral cancers have shown that targeting this complex can successfully induce peptide-specific cytotoxic T lymphocytes and, in some cases, lead to clinical stabilization or tumor regression (UMIN000000905; AMED).

Other names

Survivin-2B80-88 TCRHLA-A24-restricted survivin-2B TCRAYACNTSTL-specific TCRSVN-2B80-88 TCRSurvivin-2B peptide-specific T cell receptor

The TCR specifically recognizes the AYACNTSTL peptide presented by HLA-A*2402 on the surface of tumor cells. This binding event triggers the activation of the T cell, leading to the release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines such as interferon-gamma, which results in the targeted lysis of the cancer cell.