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Homing of cytokine-induced killer cells during the treatment of acute promyelocytic leukemia

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Abstract

Cytokine-induced killer (CIK) cells have been shown to be an effective immunotherapy for malignancies. However, their clinical application has been limited due to lack of knowledge on their in vivo kinesis. In this study, we explored their biodistribution by labeling CIK cells with 18F-FDG and tracking their in vivo migration by PET/CT imaging. In the nine refractory APL patients enrolled in this study, pre-treatment PET/CT scans revealed leukemia burdens in vertebrae, and the bones of the pelvis and limbs. Post-treatment serial PET/CT tracked the localization of CIK cells over time: at 1 h, the majority of these cells accumulated diffusely in the lungs, while the first minor cell activities were observed in brain, liver and spleen; at 4 and 8 h, they not only migrated to the heart, spleen, and liver, but also showed tendencies to accumulate in bone marrow and brain. This specific cell migration route suggested that CIK cells show in vivo functional kinesis and potency as a targeted immunotherapy. The clinical outcome of this small cohort of nine patients supported the efficacy of this regimen: two patients achieved rapid complete remission after three-cycle treatment, and six patients remained stable, subsequently became sensitive to conventional therapy, and also achieved complete remission.

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References

  1. Bonanno G, Iudicone P, Mariotti A, Procoli A, Pandolfi A, Fioravanti D, et al. Thymoglobulin, interferon-γ and interleukin-2 efficiently expand cytokine-induced killer (CIK) cells in clinical-grade cultures. J Transl Med. 2010;7(8):129–43.

    Article  Google Scholar 

  2. Rettinger E, Meyer V, Kreyenberg H, Volk A, Kuci S, Willasch A, et al. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models. Front Oncol. 2012;2:32.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Linn YC, Lau SK, Liu BH, Ng LH, Yong HX, Hui KM. Characterization of the recognition and functional heterogeneity exhibited by cytokine-induced killer cell subsets against acute myeloid leukemia target cell. Immunology. 2008;126:423–35.

    Article  PubMed  Google Scholar 

  4. Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med. 1991;174(1):139–49.

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt-Wolf GD, Negrin RS, Schmidt-Wolf IG. Activated T cells and cytokine-induced CD3 + CD56 + killer cells. Ann Hematol. 1997;74(2):51–6.

    Article  CAS  PubMed  Google Scholar 

  6. Olioso P, Giancola R, Di Riti M, Contento A, Accorsi P, Lacone A. Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial. Hematol Oncol. 2009;27:130–9.

    Article  CAS  PubMed  Google Scholar 

  7. Marin V, Pizzitola I, Agostoni V, Attianese GMPG, Finney H, Lawson A, et al. Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica. 2010;95(10):2144–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Wu CP, Jiang JT, Shi LR, Xu N. Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer. Anticancer Res. 2008;28:3997–4002.

    CAS  PubMed  Google Scholar 

  9. Hardy J, Edinger M, Bachmann MH, Negrin RS, Fathman CG, Contag CH. Bioluminescence imaging of lymphocyte trafficking in vivo. Exp Hematol. 2001;29:1353–60.

    Article  CAS  PubMed  Google Scholar 

  10. Edinger M, Cao Y, Verneris MR, Bachmann MH, Contag CH, Negrin RS. Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence. Blood. 2003;101:640–8.

    Article  CAS  PubMed  Google Scholar 

  11. Buck AK, Bommer M, Juweid ME, Glatting G, Stilgenbauer S, Mottaghy FM, et al. First demonstration of leukemia imaging with the proliferation marker 18F fluorodeoxythymidine. J Nucl Med. 2008;49(11):1756–62.

    Article  PubMed  Google Scholar 

  12. Stölzel F, Röllig C, Radke J, Mohr B, Platzbecker U, Bomhäuser M, et al. 18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia. Haematologica. 2011;96(10):1552–6.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Introna M, Borleri G, Conti E, Franceschetti M, Barihui AM, Broady R, et al. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007;92(7):952–9.

    Article  PubMed  Google Scholar 

  14. Kang WJ, Kang HJ, Lee DS, Chung JK, Lee MC, Lee DS. Tissue distribution of 18F-FDG labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med. 2006;47(8):1295–301.

    PubMed  Google Scholar 

  15. Dumarey N, Egrise D, Blocklet D, Stallenberg B, Remmelink M, dal Marmol V, et al. Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients. J Nucl Med. 2006;47(4):625–32.

    PubMed  Google Scholar 

  16. Huang W, Sun GL, Li XS, Cao Q, Lu Y, Jang GS, et al. Acute promyelocytic leukemia: clinical relevance of two major PML/RARα isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse. Blood. 1993;82:1264–9.

    CAS  PubMed  Google Scholar 

  17. Liu P, Tarlé SA, Hajra A, Claxton DF, Marlton P, Freedman M, et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science. 1993;261(5124):1041–4.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Ellen Wertheimer and Dr. Richard C. Reba for editing assistance. This clinical trial is supported by China National Natural Science Foundation NO.81070439, and China 863 Projects Foundation No. 2012AA020903.

Conflict of interest

The authors declare no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within that could inappropriately influence (bias) their work.

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Authors and Affiliations

  1. Department of Hematology and Central Laboratory, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China

    Hong Wang, Fenglin Cao, Jinmei Li, Xiuhua Liu, Zhiyu Liu, Yang Li, Hui Zhao & Jin Zhou

  2. Heilongjiang Institute for Hematology and Oncology Researches, Harbin, China

    Fenglin Cao, Lifan Wang & Jin Zhou

  3. Department of PET/CT, First Affiliated Hospital, Harbin Medical University, Harbin, China

    Yong Li

Authors
  1. Hong Wang
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  2. Fenglin Cao
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  3. Jinmei Li
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  4. Yong Li
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  5. Xiuhua Liu
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  6. Lifan Wang
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  7. Zhiyu Liu
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  8. Yang Li
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  9. Hui Zhao
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  10. Jin Zhou
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Corresponding author

Correspondence to Jin Zhou.

Additional information

This study was registered at http://www.isrctn.org identifier: ISRCTN25421117.

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Wang, H., Cao, F., Li, J. et al. Homing of cytokine-induced killer cells during the treatment of acute promyelocytic leukemia. Int J Hematol 100, 165–170 (2014). https://doi.org/10.1007/s12185-014-1618-7

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  • DOI: https://doi.org/10.1007/s12185-014-1618-7

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