Hepatitis C virus non-structural protein 3-specific T-cell receptor (HCV NS3-specific TCR)

The T cell receptor (TCR) recognizing HCV NS3-derived peptide–MHC complexes is a specialized immune receptor engineered or isolated to target cells infected with the Hepatitis C Virus (HCV) or HCV-associated malignancies. It specifically binds to epitopes derived from the Non-Structural protein 3 (NS3) of HCV, such as the immunodominant NS3:1073–1081 or NS3:1406–1415 peptides, when presented by Major Histocompatibility Complex (MHC) class I molecules, most commonly HLA-A*02:01. This recognition triggers a potent immune response, including the release of cytotoxic granules and pro-inflammatory cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which facilitate the destruction of target cells. In the context of therapeutic development, this TCR is utilized in TCR-engineered T-cell (TCR-T) therapy, where a patient's own T cells are modified to express the high-affinity receptor. Specific examples include the HCV1406 TCR, which has shown the ability to mediate regression of established HCV-positive tumors in preclinical models. This approach is particularly relevant for treating HCV-related hepatocellular carcinoma (HCC), where traditional direct-acting antivirals (DAAs) may clear the virus but do not eliminate existing tumor cells. Clinical and preclinical studies have demonstrated that these TCR-T cells can mediate significant tumor regression and viral clearance. However, challenges such as cytokine release syndrome (CRS) and the potential for viral escape through epitope mutation remain key considerations in the clinical application of this technology.

Other names

T cell receptor recognizing HCV NS3-derived peptide–MHC complexesHCV NS3-specific T-cell receptorNS3-specific TCRHCV1406 TCRNS3:1073-1081 TCRHCV-specific TCRHCV NS3-specific TCR-T

Engineered T cells expressing the TCR recognize specific HCV NS3 peptides presented by HLA-A2 on infected or malignant cells, leading to T-cell activation, cytokine release, and targeted cell lysis.