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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.  

Clinical Application

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.

Publications

Nonlytic Lymphocytes Engineered to Express Virus-Specific T-Cell Receptors Limit HBV Infection by Activating APOBEC3

Koh S et al. Gastroenterology (2018)

T-cell therapy for chronic viral hepatitis

Bertoletti A et al. Cytotherapy (2017)

Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection

Kah J et al. Journal of Clinical Investigation (2017)

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)

TCRs in Development

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.

pipeline