T-cell receptor recognizing Hepatitis B virus PreS2 and core epitopes (HBV-specific TCR)

T-cell receptors (TCRs) recognizing Hepatitis B virus (HBV) PreS2 and core epitopes are specialized immune receptors utilized in adoptive cell transfer (ACT) therapies to treat chronic HBV infection and HBV-associated hepatocellular carcinoma (HCC) [1]. These TCRs are engineered to bind with high affinity to specific viral peptides, such as those derived from the PreS2 surface protein or the core antigen (HBcAg), when presented by Human Leukocyte Antigen (HLA) molecules on the surface of target cells [2]. By modifying a patient's own T cells to express these TCRs, the therapy bypasses the natural immune exhaustion characteristic of chronic hepatitis B, enabling the immune system to recognize and eliminate infected hepatocytes and tumor cells containing integrated HBV DNA [3]. This approach not only targets the virus directly but also addresses the underlying cause of HBV-related malignancy by clearing cells with oncogenic viral integrations [4]. Clinical developments, such as SCG101, focus on specific epitopes like PreS2 to maximize therapeutic efficacy and achieve a functional cure for HBV [5]. Sources: [1] Tan, A. T., et al. (2021). "T cell receptor-redirected T cells for the treatment of HBV-related hepatocellular carcinoma." Gastroenterology. [2] Gehring, A. J., et al. (2011). "Engineering self-antigen specific T cells for gene therapy of hepatocellular carcinoma." Journal of Hepatology. [3] SCG Cell Therapy. (2023). "SCG101: A First-in-Class Autologous TCR-T Cell Therapy." [4] Boni, C., et al. (2007). "Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection." Journal of Virology. [5] ClinicalTrials.gov. (2022). "A Study of SCG101 in Patients With HBV-Related Hepatocellular Carcinoma." NCT05417932.

Other names

HBV-specific T-cell receptorPreS2-specific TCRCore-specific TCRHBV-TCRAnti-HBV TCRHepatitis B virus-specific T-cell receptor

Engineered T-cell receptors facilitate the recognition of HBV-derived peptides (such as PreS2 or Core epitopes) presented by HLA-A*02:01 or other MHC molecules, triggering T-cell activation, secretion of antiviral cytokines like IFN-gamma, and direct cytolytic destruction of HBV-infected or HBV-integrated cells [1, 2].