Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice

ABSTRACT

Background: The response of hepatocellular carcinoma (HCC) to immunotherapy is often disappointing and new strategies are clearly needed. The aim of the present study was to investigate whether cytokine-induced killer (CIK) cells combined with a dendritic cell vaccination enhanced cytotoxicity against hepatocarcinoma tumor cells in an in vivo animal model.

Methods: CIKs and DCs were prepared from C3H/HeJ mice by conventional methods, the dendritic cell (DC) pulsed with a MH134 cell lysate, DC or CIK alone were used as controls. Cell phenotypes were analyzed by flow cytometry, cytokine secretion levels were determined by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was assessed by means of an in vitro lactate dehydrogenase (LDH) release assay. A mouse hepatocarcinoma cell MH134-bearing mice model was established to test the in vivo anti-tumor efficacy of the system.

Results: CIK cells combined with DC therapy resulted in significant inhibition of tumor growth compared with the control group, whereas the decrease in tumor growth in mice that had been treated with CIK or DC alone did not reach the level of statistical significance. The combination therapy led to a further increase in the population of cytotoxic T cells (CTLs) in vivo, compared to the CIK or DC alone therapy. In addition, the combination therapy significantly enhanced cytotoxic activity against MH134 cells.

Conclusion: Taken together, these results show that a DC + CIK vaccination is more effective than DC or CIK alone therapy for the treatment of hepatocarcinoma cancer.

KEYWORDS:

• Cytokine-induced killer cells
• dendritic cells
• hepatocellular carcinoma

Declaration of interest

There is no conflict of interest for any of the authors. The authors alone are responsible for the content and writing of the paper.

Funding

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. HN14C0082).

Additional information

Funding

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. HN14C0082).