T cell receptor recognizing NA17-A peptide in complex with HLA-A*02:01 (TCR-NA17-A/HLA-A*02:01)

The T cell receptor (TCR) recognizing the NA17-A peptide in complex with HLA-A*02:01 is a specialized immune receptor utilized in the development of adoptive cell therapies for cancer. NA17-A is a tumor-associated antigen derived from an alternative transcript or intron of the N-acetylglucosaminyltransferase V (GnT-V or MGAT5) gene, which is highly expressed in a significant percentage of melanoma cases (Guilloux et al., 1996, J. Exp. Med.). This specific TCR is engineered into a patient's own CD8+ T cells to enable them to identify and eliminate cancer cells that present the NA17-A peptide via the HLA-A*02:01 major histocompatibility complex. Upon recognition of the peptide-MHC complex, the TCR initiates a signaling cascade that results in T-cell proliferation and the targeted lysis of melanoma cells. While this approach offers a high degree of specificity for tumor cells, therapeutic challenges include the potential for off-target toxicity if the antigen is expressed in healthy tissues and the risk of cytokine release syndrome following T-cell activation. Clinical research into NA17-A TCR-T therapies aims to provide a potent treatment option for patients with metastatic melanoma who are HLA-A*02:01 positive (Kawakami et al., 1994, PNAS).

Other names

NA17-A TCRGnT-V TCRN-acetylglucosaminyltransferase V TCRNA17-A/A2 TCRMelanoma antigen NA17-A specific T cell receptor

The TCR specifically recognizes and binds to the NA17-A peptide (VLPDVFIRC) presented by the HLA-A*02:01 MHC class I molecule on the surface of tumor cells. This binding event triggers the CD3 signaling complex, leading to T-cell activation, secretion of pro-inflammatory cytokines (e.g., IFN-gamma, TNF-alpha), and the release of perforin and granzymes that induce apoptosis in the target melanoma cell (Guilloux et al., 1996, J. Exp. Med.).