Patient-derived dendritic cells transduced with an a-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells.
OBJECTIVE
Breaking immunologic tolerance towards the hepatocellular carcinoma (HCC)-associated alpha-fetoprotein (AFP) antigen is possible. The use of this potential for the treatment of immunocompromised HCC patients is limited. In this study, we analyzed whether dendritic cells (DCs) from HCC patients transduced with a human AFP (hAFP)-expressing adenovirus and co-cultured with cytokine-induced killer (CIK) cells can induce a strong specific immune response against HCC-cells.


METHODS
An hAFP-encoding adenovirus (Ad-hAFP) was generated. DCs from healthy donors or patients were transduced at a very high efficacy. Afterwards, DCs were co-cultured with autologous CIK-cells, and their ability to lyse HCC-cells was analyzed.


RESULTS
AFP-transduced DCs stimulated CIK cells strongly to lyse about 70% of AFP-expressing HCC cells. Cytotoxicity was significantly higher when lymphocytes were co-cultured with Ad-hAFP-transduced DCs than with Ad-mock-transduced DCs, indicating an AFP-specific immune response. More interestingly, CIK cells from patients with AFP-positive HCC could be stimulated to lyse AFP-expressing HCC cells as effectively as CIK cells from healthy individuals and stronger than CIK cells from patients without AFP-expressing HCC.


CONCLUSIONS
The data demonstrate that patient-derived DCs that were transduced with an AFP-expressing adenovirus and co-cultured with autologous CIK cells induce an AFP-specific, strong immune response against HCC cells. Therefore, this approach may have a potential for an adoptive and/or DC-based immunotherapy for HCC patients.
González-Carmona
Maria A
MA
Department of Medicine I, University of Bonn, Bonn, Germany.
Märten
Angela
A
Hoffmann
Per
P
Schneider
Carlo
C
Sievers
Elisabeth
E
Schmidt-Wolf
Ingo G H
IG
Sauerbruch
Tilman
T
Caselmann
Wolfgang H
WH
D000256:Adenoviridae; D019264:Adoptive Transfer; D017951:Antigen Presentation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D014161:Transduction, Genetic; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000276:immunology* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D016207:Cytokines; D006680:HLA Antigens; D000509:alpha-Fetoproteins