Page 64 - ebook HCC

62 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 63
FEBRUARY 13 - 16, 2014

TRANSARTERIAL CHEMOEMBOLISATION GENERATION OF RAPID AND POTENT ANTI-
FOR HEPATOCELLULAR CARCINOMA CAN TUMOR IMMUNITY USING MICROSPHERE-
MODULATE REGULATORY CD4+T-CELLS BASED PRIME BOOST T CELL VACCINES

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Ka-Kit Li , Yazid J. Resheq , Stuart M. Curbishley , Tony Bruns , Thomas C. Wirth , Dmitrij Ostroumov , Michael P. Manns 1
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Henning W. Zimmermann , Palak J. Trivedi , Christopher J. Weston , David H. Adams 1 1 Gastroenterology, Hepatology and Endocrinology, Medical School Hannover,
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1 University of Birmingham, NIHR Biomedical Research Unit & Centre for Liver Research, 30625 Hannover, Germany
Birmingham, United Kingdom, University of Jena, Integrated Research and Treatment
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Center for Sepsis Control and Care, Jena, University of Aachen, Department of Corresponding author’s e-mail: Wirth.Thomas@mh-hannover.de
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Medicine III, Aachen, Germany, NIHR Biomedical Research Unit & Centre for Liver
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Research, University of Birmingham, Birmingham, United Kingdom
Introduction: Due to disadvantages and limitations of current dendritic cell vaccinations,
Corresponding author’s e-mail: k.li.2@bham.ac.uk immunotherapeutic cancer treatment requires novel, innovative vaccination strategies
that are able to rapidly generate high numbers of cancer-specific CD8 T cells. Current
vaccinations, however, fail to generate potent immune responses that allow for long-term
BASIC SPEAKERS ABSTRACTS TACE may enhance anti-tumour immune-response. CD4 regulatory T-cells (CD4 Treg) Aims: The aim of our study was to establish a novel vaccination method that allows for BASIC SPEAKERS ABSTRACTS
tracking and phenotyping of cancer-specific CD8 T cells.
Introduction: Transarterial chemoembolisation (TACE) delivers local-regional
chemotherapy for patients with hepatocellular carcinoma (HCC) and evidence suggests
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the induction of potent immune responses in vivo. Our primary goal was a rapid induction
are immunosuppressive T-cells crucial for the maintenance of immune-homeostasis
of fully functional and cytotoxic CD8 T cells and to test them in a model system of
which, in the context of cancer, inhibit effective anti-tumour immunity.
autochthonous murine liver cancers.
Aims: The aims of this study were to investigate whether TACE alters the number and
function of CD4 Treg in patients with HCC.
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hydrodynamic tail vein injection of transposon-flanked plasmids in conjunction with a
transiently expressed transposase. Using this flexible plasmid-based system, we were
Methodology: Blood was collected from patients with HCC (n=50) before, 3 days and Methodology: We established an in vivo model of hepatocellular carcinoma using
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42 days after TACE. The frequency of CD4 Treg was determined by flow-cytometry, and able to establish orthotopic liver cancers and to incorporate model antigens and in vivo
direct suppressive-capacity assessed through co-culture proliferation assays with effector monitoring genes. In parallel, we tested various immunization protocols that employed
T-cells. Patients were assessed for response to TACE according to the mRECIST criteria injection of antigen coupled to PLGA microspheres and different bacterial and viral
by cross-sectional imaging. vaccination vectors to identify the optimal combination for prime-boost vaccinations.
Results: The proportion of Treg within the total CD4 T-cell population was significantly Results: Our results show that administration of the model antigen ovalbumin coupled
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reduced by day 3 in patients following TACE (baseline; 7.9%+4.8%, day 3; 6.4%+4.2%, to biodegradable PLGA microspheres induces tumor-specific CD8 T cell populations that
day 42; 6.1%+3.9%, P<0.05). When patients were stratified according to treatment effect; can rapidly be boosted to high numbers in vivo when followed by booster vaccination with
Treg frequencies were significantly reduced following TACE in treatment-responders/ a Listeria monocytogenes vector. This novel vaccination regime resulted in fully functional
stable disease (n=40; baseline; 8.4%+4.9%, day 42; 5.8%+4.0%, P<0.05). When and oncolytic CD8 T cell populations within 14 days. In our newly established in vivo
compared to patients with progressive disease, Treg frequencies were significantly model of hepatocellular carcinoma, the novel vaccination regime resulted in eradication
increased following TACE (n=10; baseline; 5.0%+3.1%, day 42; 7.7%+2.7%, P>0.05). of autochthonous liver cancers and in significantly improved overall survival of the treated
CD4 Treg from HCC patients suppressed effector T-cell proliferation and this suppressive mice compared to a conventional dendritic cell vaccine.
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ability was comparable before and after TACE irrespective of treatment-response.
Conclusions: Tumor vaccines based on a prime-boost protocols employing PLGA
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Conclusions: Treatment response to TACE was correlated with a reduction in CD4 Treg microsphere administration and subsequent Listeria vector vaccination holds promise as
in patients with HCC. This may be used as a predictor of TACE treatment-response and a novel immunotherapy for hepatocellular carcinoma.
might represent the basis to support the use of TACE as an adjuvant to immunotherapy.