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64 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 65
FEBRUARY 13 - 16, 2014

THERAPY WITH T CELL RECEPTOR GENE
MODIFIED T CELLS TARGETING HCC WITH
HBV-DNA INTEGRATION

Waseem Qasim , Maurizia Brunetto , Adam Gehring , Shao-An Xue , Atefeh Khakpoor Results: Cytoplasmic HBsAg was detected in explanted HCC and recurrent metastases
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6 , Hong Zhan , Pietro Ciccorossi , Kimberly Gilmour , Daniela Cavallone , Francesco but not in the transplanted liver. Infusion of TCR-redirected lymphocytes was well tolerated
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Moriconi , Farzin Farzhenah , Alessandro Mazzoni , Lucas Chan , Emma Morris , without significant adverse events. Transaminase levels showed a steady (but clinically
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Adrian Thrasher , Mala Maini , Ferruccio Bonino , Hans Stauss , Antonio Bertoletti 6 3 non-significant) increase (19, 70, 81, 106 IU/L) at day 0, 3, 10, 30 after T cell transfer,
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1 Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom, while serum HBsAg decreased over the same time period (3561, 3150, 2631, 554 IU/ml).
2 Hepatology Unit, University Hospital of Pisa, Pisa, Italy, Singapore Institute for Clinical AFP levels dropped after infusion (4569 to 2949 ng/ml at day 10) but then increased at
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Sciences, A*STAR, Singapore, Singapore, Molecular Microbiology and Immunology day 30 (6389 ng/ml). TCR-redirected cells were detected at a frequency of 6%> of total
Department, Saint Louis University School of Medicine, St. Louis, United States, CD8 T cells after 30 days indicating notable in vivo expansion. Imaging analysis performed
5 Department of Immunology, Royal Free Hospital, London, United Kingdom, Emerging 40 days after therapy did not detect any measurable reduction in the size of pre-existing
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BASIC SPEAKERS ABSTRACTS Corresponding author’s e-mail: antonio@sics.a-star.edu.sg Conclusions: HBV antigens was expressed in HCC relapses occurring in a liver BASIC SPEAKERS ABSTRACTS
metastasis and progressive CNS lesions resulted in death at day 60.
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Viral Diseases, Duke-NUS Medical School, Singapore, Singapore, Rayne Institute,
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Kings College, London, United Kingdom, General Medicine, Liver – Digestive Division ,
University Hospital of Pisa, Pisa, Italy
transplanted patient and were recognized in vivo by lymphocytes engineered to express
HBV-specific T cell receptors. These T cells were able to survive, expand and mediate
a reduction in HBsAg without exacerbation of liver inflammation. Whilst clinical benefit
was not demonstrated in this patient who was treated on a compassionate basis in the
Introduction: HBV-DNA integration frequently occurs in HBV-related HCC, but whether
HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic
constitute a new therapeutic opportunity in the early treatment of HCC relapses in liver
transplant patients.
strategies remains controversial context of end-stage metastatic disease, these data show that gene –modified T cells can
Aims: We characterized HBV antigen expression in HCC metastasis occurring in a patient
who underwent liver transplantation for HBV-related HCC. We then used HBsAg-specific
T cell receptor redirected T cells to treat the chemoresistant extrahepatic metastases
present in the patient.
Methodology: Biopsies of the primary HCC, lymphonodes metastasis and transplanted
liver were analyzed for HBV antigen expression with immune-histology methods and for
HBV-DNA integration. T cell receptors specific for the HLA-A201/HBs183-91 complex were
utilized to redirect the T cell specificity of the patient lymphocytes using retroviral vector
produced under GMP conditions. The redirected T cells were administered as a single
dose at 10,000 HBs183-91 specific T cells/kg and the patient underwent serial virological,

biochemical and radiological monitoring assessments.