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Human Cytokine-Induced Killer Cells Inhibit the Growth of Hepatocellular Carcinoma Cells Transplanted in Nude Mice
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Abstract:
Objective: To investigate the inhibitory effects of the cytokine-induced killer (CIK) cells from human peripheral blood mononuclear cells (PBMCs) origin on the growth of hepatocellular carcinoma (HCC) cells in animal model. Methods: PBMCs from healthy donors were enriched by using the specific program of the Cobe Spectra blood separator and induced in vitro into CIK cells in serum-free culture medium containing interferon-gamma (IFN-γ), interleukin-2 (IL-2)，and anti-CD3. The phenotypes and characterization of CIK cells were identified by flow cytometric analysis. BALB/c nude mice subscapularly transplanted with 1.5×105 of BEL-7402 HCC cell at the exponential growth produced 100% tumor incidence and were treated with human CIK cells for consecutive six days on the second day after HCC transplantation. Results:The CIK cells identified by flow cytometric analyses were shown to be a heterogeneous population with different cellular phenotypes. The total CIK cells and CD3+/CD56+ positive cells significantly increased by 7 fold and 6-fold, respectively, in cell proliferation number at day 13 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells. In tumor-bearing nude mice, human CIK cells showed a significant inhibitory effect on the growth of transplanted HCC, resulting in a statistical significant difference among the treated and control groups. There was dose-response dependent relationship between the inhibitory effect and number of treated CIK cells. Conclusion: Human CIK cells are of highly efficient cytotoxic effector cells against hepatocellular carcinoma cells in murine model and are likely to be used as an immune therapeutic strategy for HCC patients
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