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.
Immunosuppressive Drug Resistant Armored TCR T cells for immune-therapy of HCC in liver transplant patients
Hafezi et al. Hepatology (2020)
Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy
Tan AT et al. Gastroenterology (2019)
Nonlytic Lymphocytes Engineered to Express Virus-Specific T-Cell Receptors Limit HBV Infection by Activating APOBEC3
Koh S et al. Gastroenterology (2018)
Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection
Kah J et al. Journal of Clinical Investigation (2017)
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.