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Cytotherapy. 2015 Aug;17(8):1139-51. doi: 10.1016/j.jcyt.2015.04.011. Epub 2015 Jun 10.

Cytomegalovirus-specific cytokine-induced killer cells: concurrent targeting of leukemia and cytomegalovirus.

Author information

1
Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany. Electronic address: verena.pfirrmann@kgu.de.
2
Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt/Main, Germany.
3
Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
4
Institute for Transfusion Medicine and Immunohematology and German Red Cross Blood Donor Service, University Hospital Frankfurt, Goethe University, Baden-Wuerttemberg-Hessen, Frankfurt/Main, Germany.
5
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt/Main, Germany.
6
Institute for Experimental Cancer Research in Pediatrics, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
7
Division of Allergology, Pneumology and Cystic Fibrosis, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
8
Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany. Electronic address: peter.bader@kgu.de.

Abstract

BACKGROUND AIMS:

Human cytomegalovirus (CMV) infection and reactivation is a leading complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition to drug treatment, the adoptive transfer of virus-specific T cells to restore cellular immunity has become a standard therapy after allogeneic HSCT. We recently demonstrated potent anti-leukemic activity of interleukin (IL)-15-activated cytokine-induced killer (CIK) cells. With the use of the same expansion protocol, we asked whether concurrent CMV antigen-pulsing might generate CIK cells with anti-leukemic and anti-CMV activity.

METHODS:

CIK cells expanded in the presence of interferon-γ, IL-2, IL-15 and anti-CD3 antibody were pulsed once with CMV(pp65) peptide pool. CMV-specific CIK (CIK(pp65)) and conventional CIK cells were phenotypically and functionally characterized according to their cytokine secretion pattern, degranulation capacity and T-cell receptor (TCR)-mediated and NKG2D-mediated cytotoxicity.

RESULTS:

We demonstrated that among CIK cells generated from CMV-seropositive donors, a single stimulation with CMV(pp65) protein co-expanded cytotoxic CMV-specific cells without sacrificing anti-tumor reactivity. Cells generated in this fashion lysed CMV(pp65)-loaded target cells and CMV-infected fibroblasts but also leukemic cells. Meanwhile, the alloreactive potential of CIK(pp65) cells remained low. Interestingly, CMV reactivity was TCR-mediated and CMV-specific cells could be found in CD3(+)CD8(+)CD56(+/-) cytotoxic T-cell subpopulations.

CONCLUSIONS:

We provide an efficient method to generate CIK(pp65) cells that may represent a useful cell therapy approach for preemptive immunotherapy in patients who have both an apparent risk of CMV and impending leukemic relapse after allogeneic stem cell transplantation.

KEYWORDS:

CIK cells; CMV; cytotoxicity; immunotherapy; leukemia

PMID:
26072027
DOI:
10.1016/j.jcyt.2015.04.011
[Indexed for MEDLINE]

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