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January 25, 2017

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January 25, 2017

New publication –  Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient

Dr. Antonio Bertoletti and his research team, in collaboration with research teams from University College London, University Hospital of Pisa, and Kings College, London, have conducted T-cell immunotherapy in a patient with HBV-related hepatocellular carcinoma. This initial clinical trial demonstrated ‘the feasibility of providing autologous TCR-redirected therapy against hepatocellular carcinoma’, supporting the potential of TCR-T cell therapy in clinical applications against other chronic viral infection and the related complications (e.g. cancer).

Abstract – HBV-DNA integration frequently occurs in HBV-related hepatocellular carcinoma (HCC), but whether HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic strategies remains controversial. Here, we first characterized HBV antigen expression in HCC metastases, occurring in a patient who had undergone liver transplantation for HBV-related HCC. We then deployed for the first time in HCC autologous T cells, genetically modified to express an HBsAg specific T cell receptor, as therapy against chemoresistant extrahepatic metastases. We confirmed that HBV antigens were expressed in HCC metastases (but not in the donor liver) and demonstrated that tumour cells were recognized in vivo by lymphocytes, engineered to express an HBV-specific T cell receptor (TCR). Gene-modified T cells survived, expanded and mediated a reduction in HBsAg levels without exacerbation of liver inflammation or other toxicity. Whilst clinical efficacy was not established in this subject with end-stage metastatic disease, we confirm the feasibility of providing autologous TCR-redirected therapy against HCC and advocate this strategy as a novel therapeutic opportunity in hepatitis B-associated malignancies. PubMed