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P07.02-YI

HETEROLOGOUS IMMUNE VACCINATION INDUCES
SPECIFIC THERAPEUTIC CD8 T-CELL IMMUNE
RESPONSES AGAINST TUMOR-ASSOCIATED
ANTIGEN ALPHA-FETOPROTEIN EXPRESSED IN
HEPATOCELLULAR CARCINOMA

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1
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Steven S. Duong , Jessica Wingerath , Dmitrij Ostroumov , Norman Woller ,
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Florian Kühnel , Michael P. Manns , Thomas C. Wirth 1
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1
1 Gastroenterology, Hepatology and Endokrinology, Hannover Medical School, Hannover,
Germany
Corresponding author’s email: duong.steven@mh-hannover.de
Introduction: CD8 T cells are a major component of the adaptive immune system
and responsible for the recognition and elimination of malignant cells by major
histocompatibility complex class I (MHCI)-restricted cytotoxicity. Immunotherapies are
capable of inducing potent immune responses against tumour-associated antigens (TAA). ePOSTER ABSTRACTS
The TAA alpha-fetoprotein (AFP) is highly upregulated in hepatocellular carcinoma
(HCC) and serves as a diagnostic marker and as a potential target for immunotherapies.

Aims: The aim of this project is the establishment of a therapeutic AFP-specific
heterologous immune therapeutic vaccination protocol targeting HCC.

Material and Methods: An orthotopic HCC mouse model was established in vivo using
the ‘Sleeping Beauty’ transposon system. Hydrodynamic injection was performed to
transfect murine hepatocytes with plasmids containing oncogenic NRas G12V linked to
murine AFP (mAFP) in combination with myristoylated Akt1 and short hairpin against
p53 (shRp53). High-affinity binding mAFP epitopes were optimized by EpitOptimizer to
further improve binding affinity to MHCI molecules. A heterologous vaccination protocol
consisting of primary dendritic cell immunization followed by a boost with soluble
heteroclitic mAFP peptide, Poly I:C and an agonistic CD40 antibody will be performed
in tumour-bearing mice.

EASL HCC Summit • Geneva, Switzerland • 2-5 February, 2017 245