Immune Netw.  2012 Dec;12(6):247-252. 10.4110/in.2012.12.6.247.

Inhibition of Human Pancreatic Tumor Growth by Cytokine-Induced Killer Cells in Nude Mouse Xenograft Model

• Kim JS
• Park YS
• Kim JY
• Kim YG
• Kim YJ
• Lee HK
• Kim HS
• Hong JT
• Kim Y
• Han SB

• KMID: 2150756
• DOI: http://doi.org/10.4110/in.2012.12.6.247

Abstract

Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% CD3+, 4% CD3-CD56+, 41% CD3+CD56+, 11% CD4+, and 73% CD8+. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100:1, CIK cells destroyed 51% of AsPC-1 human pancreatic cancer cells, as measured by the 51Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.

Keyword

Pancreatic cancer; Adoptive immunotherapy; Cytokine-induced killer cells

MeSH Terms

Animals
Cytokine-Induced Killer Cells
Humans
Immunotherapy, Adoptive
Mice
Mice, Nude
Pancreatic Neoplasms
Transplantation, Heterologous

Figure

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  Figure 1 The phenotypes of CIK cells. Human PBMCs were cultured in the presence of IL-2 and anti-CD3 antibody for 14 days and the resulting CIK cell populations were stained with human monoclonal antibodies, such as anti-CD3-FITC plus anti-CD56-PE (A), anti-CD4-FITC plus anti-CD8-PE (B).

• 

  Figure 2 The in vitro cytotoxicity of CIK cells. Human PBMCs were cultured in the presence of IL-2 and anti-CD3 antibody for 14 days and the resulting CIK cell populations were used to examine cytotoxicity to K562 (A) and AsPC-1 (B). These target cells were labeled with 51Cr and incubated for 4 h with CIK cells at effector-to-target ratios of 1-100:1.

• 

  Figure 3 Inhibition of AsPC-1 tumor growth by CIK cells in nude mouse xenograft models. Nude mice (n=7) were implanted subcutaneously with nine million AsPC-1 cancer cells. CIK cells at doses of 1 (CIK 1), 3 (CIK 3), and 10 (CIK 10)×106 cells/mouse were injected intravenously once a week. Adriamycin (ADR) was injected intravenously at 2 mg/kg. Tumor volumes were estimated by the formula: length (mm)×width (mm)×height (mm)/2 (A). On day 20, the mice were sacrificed and the tumor weights were measured (B). Representative photographs are shown (C). Statistical significance was determined using the ANOVA test versus PBS-treated control group (*p<0.05, **p<0.01).

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  Figure 4 Body weight changes of tumor-bearing nude mice. Nude mice (n=7) were implanted subcutaneously with nine million AsPC-1 cancer cells. CIK cells at doses of 1 (CIK 1), 3 (CIK 3), and 10 (CIK 10)×106 cells/mouse were injected intravenously once a week. Adriamycin (ADR) was injected intravenously at 2 mg/kg. The body weights of the tumor-bearing nude mice were measured to estimate toxicity.

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