We have developed the capability to engineer Hepatitis B virus (HBV)-specific T cells that can recognize HBV-expressing tumor cells and achieve targeted killing.HBV is the major etiologic agent for hepatocellular carcinoma (HCC) development, accounting for at least 50% cases of HCC worldwide and at least 80% of cases in Asia. HBV predisposes to the development of HCC by causing chronic inflammation and genome destabilization after DNA integration into the genome of hepatocytes.
More than 80% of HBV-related HCC tumors have detectable HBV-DNA integration. Epitopes encoded by these integrated HBV-DNA can be assembled with major histocompatibility complex (MHC) class I molecules on cell surfaces and serve as ideal targets for T cells.
LioCyx-M is produced following current good manufacturing practice (cGMP) compliant principles in less than 2 weeks for clinical use. The general steps are as follows:
1. The patient undergoes leukapheresis to isolate white blood cells.
2. T cells from the patient are expanded and activated in Lion TCR’s GMP cell production facility.
3. Genetic material encoding our virus- or cancer-targeting TCR are introduced into the activated T cells by or electroporation.
4. The patient’s T cells now express the relevant TCR that target virus-infected or virus-related cancer cells.
5. Following phenotypic and functional validation, the TCR engineered T cells are infused back to the patient.
Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient
Qasim W et al. Journal of Hepatology (2015)
T cell receptor-therapy in HBV-related hepatocellularcarcinoma
Bertoletti A et al. Oncoimmunology (2015)
Immunoprevalence and immunodominance of HLA-Cw∗ 0801-restricted T cell response targeting the hepatitis B virus envelope transmembrane region
Tan AT et al. Journal of Virology (2014)
Building and optimizing a virus-specific T cell receptor library for targeted immunotherapy in viral infections
Banu N et al. Scientific Reports (2014)
A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus
Koh S et al. Molecular Therapy - Nucleic Acids (2013)
Our library of TCRs recognizes viral peptides expressed on MHC Class I restricted for the Asian population.
We are actively extending our proprietary TCR therapy platform to target more viruses, particularly those prevalent in Asia, for example, HBV, EBV and CMV.