TCR-T cell therapy presents special advantages when used against viral-related cancers, such as hepatitis B virus (HBV)-related liver cancer, and Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. Our library of TCRs recognizes viral peptides expressed on MHC Class I restricted for the Asian population. Currently, our proprietary TCR-T cell technology has been applied clinically against chronic HBV infection-related hepatocellular carcinoma, which is a pertinent problem in Asia. In our preclinical and clinical studies, TCR-T cell therapy is shown to be safe and specifically targets HBV-related hepatocellular carcinoma, preventing cancer cell seeding and achieving tumor regression1,2.
Our TCR-T cells are engineered to target virus-derived peptides presented on MHC class I on the surface of virus-infected cells (I) or virus-related cancer cells (II).
I Virus-infected Cells
Upon virus infection, viral proteins are expressed in the infected cells. These viral proteins are degraded into viral peptides and assembled with MHC class I to be presented onto the cell surface. These peptide-MHC I complexes on the infected cell surface are recognized by cytotoxic T cells, leading to the release of cytokines and triggering antiviral responses. However, patients suffering from chronic viral infection may only elicit a weak antiviral response due to the exhaustion of virus-specific cytotoxic T cells3. To circumvent this, we can engineer the patient’s T cells to express high-avidity TCRs using our proprietary TCR platform, leading to potent antiviral responses.
II Virus-related Cancers
Chronic viral infection predisposes a person to the development of cancer by causing repetitive tissue damage, inflammation and viral gene integration into the host genome4. The integrated viral genes can be expressed by the host mechanism to give virus-derived protein fragments, which are then degraded into viral peptides and assembled with MHC class I to be presented onto the cell surface. These cancer cells are therefore specifically labeled by viral peptides that serve as tumor antigens. Our highly specific and efficient antitumor therapy utilizes this unique feature of virus-related cancers. Using our proprietary TCR platform, we engineer the patient’s T cells with high-avidity antiviral TCRs which recognize the tumor-specific viral peptides, leading to the release of cytolytic molecules and the lysis of cancer cells.
2 Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. Qasim W et al. J Hepatol. 2015
4 Epidemiology of viral hepatitis and hepatocellular carcinoma. El-Serag HB. Gastroenterology. 2012
- The patient undergoes leukapheresis to isolate white blood cells.
- T cells from the patient are expanded and activated in Lion TCR’s GMP cell production center.
- Genetic material encoding our virus- or cancer-targeting TCR are introduced into the activated T cells by viral transduction or electroporation.
- The patient’s T cells now express the relevant TCR that target virus-infected or virus-related cancer cells.
- Following phenotypic and functional validation, the TCR engineered T cells are infused back to the patient.