Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612759
Lectures Session IV Tumors, Liver Surgery and Transplantation – Saturday, January 27, 2018, 9:15am – 10:00am, Lecture Hall A
Georg Thieme Verlag KG Stuttgart · New York

rLCMV vectors elicit tumour directed immune responses, inhibit tumour progression and prolong survival of mice

J Wingerath
1   Hannover Medical School, Gastroenterology, Hannover
,
D Ostroumov
1   Hannover Medical School, Gastroenterology, Hannover
,
M Manns
1   Hannover Medical School, Gastroenterology, Hannover
,
D Pinschewer
1   Hannover Medical School, Gastroenterology, Hannover
,
K Orlinger
1   Hannover Medical School, Gastroenterology, Hannover
,
U Berka
1   Hannover Medical School, Gastroenterology, Hannover
,
T Wirth
1   Hannover Medical School, Gastroenterology, Hannover
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Introduction:

HCC is one of the main causes of cancer related death worldwide. Personalized immune therapy against tumour associated antigens could induce potent immune responses targeting tumour cells without disastrous side effects like autoimmune disorders. Replication-deficient recombinant lymphocytic choriomeningitis virus vectors (rLCMV) carrying an antigen of interest have been shown to induce potent specific CD8 T cell immune responses in vivo with low vector directed immunity.

The aim of this study is to show if rLCMV can be used as a therapeutic approach to treat HCC.

Material and Methods:

Female C57BL/6J mice (6 – 8 wk.) were used for all experiments. rLCMV-OVA-vaccinations with 2 × 105 focus forming units (ffu) were injected intravenously. OVA-expressing HCC (OVA HCC) was generated by hydrodynamic injection (HDI) with transposon-flanked plasmids encoding ovalbumin (OVA) linked to NRasG12V, myrAkt1 and shRp53. Immune responses against the OVA-related peptide SIINFEKL were detected by flow cytometry using tetramer or intracellular cytokine staining. All results were generated under a Research Agreement with Hookipa Biotech, which provided the materials.

Results:

The suitability of rLCMV-OVA for therapy of OVA HCC was verified. It could be shown, that the tumor affected the quality of the specific CD8 T cells. However, rLCMV-OVA therapy could prolong the overall survival of the animals. Furthermore, tumor formation could be inhibited due to rLCMV-OVA vaccination before tumor induction. The present work provides many new revealing insights in the quantity and quality of rLCMV-OVA induced immune responses as well as in the usability of LCMV-based replication-deficient vectors.

Conclusion:

rLCMV is a safe replication-deficient vector which is not hampered by neutralizing antibodies. Vaccinations with rLCMV lead to efficacious protective immune responses in vivo which are highly specific against antigen of interest. Treatment with rLCMV encoding a tumour specific antigen resulted in delayed tumour progression and prolonged survival of mice. Pre-vaccinations could prevent tumour formation. Therefore, rLCMV is a promising tool for future therapy of HCC and vaccinations against tumours.