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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 Workflow

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

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)

Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellularcarcinoma cell lines

Gehring AJ et al. Journal of Hepatology (2011)

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.

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