Phenotypic characterization and anti-tumor effects of cytokine-induced killer cells derived from cord blood

Cytotherapy. 2015 Jan;17(1):86-97. doi: 10.1016/j.jcyt.2014.09.006. Epub 2014 Oct 24.

Abstract

Background aims: Cytokine-induced killer (CIK) cell therapy represents a feasible immunotherapeutic option for treating malignancies. However, the number of anti-tumor lymphocytes cannot be easily obtained from the cancer patients with poor immunity status, and older patients cannot tolerate repeated collection of blood. Cord blood-derived CIK (CB-CIK) cells have shown efficacy in treating the patients with cancer in several clinical trials. This study was conducted to evaluate the biological characteristics and anti-tumor function of CB-CIK cells.

Methods: The immunogenicity, chemokine receptors and proliferation of CB-CIK cells were analyzed by flow cytometry. The CIK cells on day 13 were treated with cisplatin and the anti-apoptosis capacity was analyzed. The function of CB-CIK cells against the human cancer was evaluated both in vitro and in vivo.

Results: Compared with peripheral blood-derived CIK (PB-CIK) cells, CB-CIK cells demonstrated lower immunogenicity and increased proliferation rates. CB-CIK cells also had a higher percentage of main functional fraction CD3(+)CD56(+). The anti-apoptosis ability of CB-CIK cells after treatment with cisplatin was higher than that of PB-CIK cells. Furthermore, CB-CIK cells were effective for secreting interleukin-2 and interferon-γ and a higher percentage of chemokine receptors CCR6 and CCR7. In addition, tumor growth was greatly inhibited by CB-CIK treatment in a nude mouse xenograft model.

Conclusions: CB-CIK cells exhibit more efficient anti-tumor activity in in vitro analysis and in the preclinical model and may serve as a potential therapeutic approach for the treatment of cancer.

Keywords: cancer; cord blood; cytokine-induced killer cells; peripheral blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cytokine-Induced Killer Cells / cytology*
  • Cytokine-Induced Killer Cells / immunology
  • Cytotoxicity, Immunologic / immunology*
  • Female
  • Fetal Blood / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / immunology*
  • Phenotype
  • Umbilical Cord / cytology

Substances

  • Interleukin-2
  • Interferon-gamma