Z Gastroenterol 2019; 57(01): e59
DOI: 10.1055/s-0038-1677204
4. Tumors
Georg Thieme Verlag KG Stuttgart · New York

Heterologous vaccinations induce potent specific CD8 T-cell immune responses against HCC-expressed tumor-associated antigens

S Duong
1   Hannover Medical School
,
S Nimanong
1   Hannover Medical School
,
D Ostroumov
1   Hannover Medical School
,
CS Falk
1   Hannover Medical School
,
MP Manns
1   Hannover Medical School
,
F Kühnel
1   Hannover Medical School
,
TC Wirth
1   Hannover Medical School
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

 

CD8 T cells play a major role in the adaptive immune system and are 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 tumor-associated antigens (TAA). TAAs alpha-fetoprotein (AFP) and glypican-3 (GPC3) are highly up-regulated in hepatocellular carcinomas (HCC) and serve as diagnostic, as well as potential targets for immunotherapies.

Aim of this project is the establishment of therapeutic TAA-specific heterologous vaccinations targeting HCC.

Flow cytometric data demonstrated a massive expansion of specific CD8 T cells against TAAs mAFP and mGPC3. Immunization with the optimized peptide resulted in a frequency of up to 30% mAFP-specific CD8 T cells of total CD8 T cells compared to < 1% after immunization with the wildtype peptide. Specific T cells were detected by intracellular cytokine staining and flow cytometry and were able to recognize native wildtype mAFP and mGPC3.

TAAs mAFP and mGPC3 are promising targets to establish effective immunotherapeutic treatments. In contrast to conventional vaccination approaches, the combination of primary dendritic cell immunization with subsequent injection of agonistic, co-stimulatory antibodies is able to massively expand tumour-specific CD8 T cells, capable of targeting AFP-expressing HCC.