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J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.

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

Author information

1
Institute of Child Health & Great Ormond Street Hospital, University College London, London, UK.
2
Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
3
Singapore Institute for Clinical Sciences, A(∗)STAR, Singapore.
4
Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, UK.
5
Program Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
6
Rayne Cell Therapy Suite, Kings College, London, London, UK.
7
General Medicine, Liver and Digestive Disease Unit, University Hospital of Pisa, Pisa, Italy.
8
Singapore Institute for Clinical Sciences, A(∗)STAR, Singapore; Program Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; School of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Edgbaston Birmingham, UK. Electronic address: antonio@duke-nus.edu.sg.

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.

KEYWORDS:

HBV-specific CD8 T cells; Liver cancer; T cell therapy

PMID:
25308176
DOI:
10.1016/j.jhep.2014.10.001
[Indexed for MEDLINE]

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