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Rettinger E, Meyer V, Kreyenberg H, 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;2:32doi: 10.3389/fonc.2012.00032.
Rettinger, E., Meyer, V., Kreyenberg, H., Volk, A., Kuçi, S., Willasch, A., Koscielniak, E., Fulda, S., Wels, W. S., Boenig, H., Klingebiel, T., & Bader, P. (2012). Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models. Frontiers in oncology, 232. https://doi.org/10.3389/fonc.2012.00032
Rettinger, Eva, et al. "Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models." Frontiers in oncology vol. 2 (2012): 32. doi: https://doi.org/10.3389/fonc.2012.00032
Rettinger E, Meyer V, Kreyenberg H, Volk A, Kuçi S, Willasch A, Koscielniak E, Fulda S, Wels WS, Boenig H, Klingebiel T, Bader P. 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 Apr 09;2:32. doi: 10.3389/fonc.2012.00032. eCollection 2012. PMID: 22655268; PMCID: PMC3356002.
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Front Oncol. 2012 Apr 09;2:32. doi: 10.3389/fonc.2012.00032. eCollection 2012.

Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models.

Frontiers in oncology

Eva Rettinger, Vida Meyer, Hermann Kreyenberg, Andreas Volk, Selim Kuçi, Andre Willasch, Ewa Koscielniak, Simone Fulda, Winfried S Wels, Halvard Boenig, Thomas Klingebiel, Peter Bader

Affiliations

  1. Department of Pediatric Hematology, Oncology and Hemostaseology, University Children's Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main Frankfurt/Main, Germany.

PMID: 22655268 PMCID: PMC3356002 DOI: 10.3389/fonc.2012.00032

Abstract

Allogeneic stem cell transplantation (allo-SCT) has become an important treatment modality for patients with high-risk acute myeloid leukemia (AML) and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD) status ultimately leading to patients' relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15-expanded cytokine-induced killer (CIK) cells may prevent relapse without causing graft-versus-host-disease (GvHD). To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL-2Rγc(-), NSG) were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS) cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow followed by liver, lung, spleen, peripheral blood (PB), and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at equal amounts were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells 250 times more CIK than THP-1 cells were needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliable 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells have potent cytotoxic capacity against AML and RMS cells without causing GvHD.

Keywords: CIK cells; NSG mice; immunotherapy; leukemia; preclinical; rhabdomyosarcoma

References

  1. Leukemia. 1999 Jan;13(1):110-8 - PubMed
  2. Cancer Res. 2002 Oct 15;62(20):5785-91 - PubMed
  3. Br J Haematol. 2005 Jul;130(1):51-7 - PubMed
  4. J Exp Med. 1991 Jul 1;174(1):139-49 - PubMed
  5. J Clin Oncol. 2004 May 1;22(9):1696-705 - PubMed
  6. Science. 2006 Mar 24;311(5768):1780-4 - PubMed
  7. Blood. 1995 Apr 1;85(7):1954-63 - PubMed
  8. J Clin Invest. 2005 Jun;115(6):1616-26 - PubMed
  9. Expert Opin Biol Ther. 2009 Jul;9(7):831-40 - PubMed
  10. Int J Cancer. 2008 Nov 1;123(9):2222-7 - PubMed
  11. Pediatr Res. 2001 Mar;49(3):332-41 - PubMed
  12. Blood. 2005 Aug 1;106(3):1113-22 - PubMed
  13. Blood. 2003 Jan 15;101(2):640-8 - PubMed
  14. Haematologica. 2010 Sep;95(9):1579-86 - PubMed
  15. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12044-9 - PubMed
  16. Cancer Res. 2004 Feb 1;64(3):1171-80 - PubMed
  17. Blood. 2011 Nov 17;118(20):5681-8 - PubMed
  18. Blood. 2008 Sep 15;112(6):2563-74 - PubMed
  19. Haematologica. 2007 Jul;92(7):952-9 - PubMed
  20. Biotechniques. 2003 Dec;35(6):1262-72 - PubMed
  21. Blood. 2011 Sep 22;118(12):3301-10 - PubMed
  22. J Neurooncol. 2002 Nov;60(2):143-50 - PubMed
  23. Nat Rev Immunol. 2007 Feb;7(2):118-30 - PubMed
  24. Int J Cancer. 2006 Sep 15;119(6):1377-82 - PubMed
  25. Bone Marrow Transplant. 1997 Feb;19(3):227-31 - PubMed
  26. J Virol. 2007 Dec;81(23):13259-64 - PubMed
  27. Exp Hematol. 2008 Nov;36(11):1487-95 - PubMed
  28. J Immunol. 2005 May 15;174(10):6477-89 - PubMed
  29. Hematol Oncol. 2009 Sep;27(3):130-9 - PubMed
  30. Blood. 2005 Sep 1;106(5):1565-73 - PubMed
  31. Nat Med. 1997 Jul;3(7):730-7 - PubMed
  32. Stem Cell Stud. 2010 Nov 23;1(1): - PubMed
  33. Leukemia. 2005 Dec;19(12):2215-22 - PubMed
  34. Blood. 2002 Nov 1;100(9):3175-82 - PubMed
  35. Int Immunopharmacol. 2007 Dec 15;7(13):1802-7 - PubMed
  36. Exp Hematol. 2004 Mar;32(3):318-24 - PubMed
  37. Cancer Res. 2004 Mar 15;64(6):2183-91 - PubMed
  38. Leukemia. 2003 Apr;17(4):760-3 - PubMed
  39. J Cancer. 2011;2:363-8 - PubMed
  40. Haematologica. 2010 Apr;95(4):651-9 - PubMed
  41. Br J Haematol. 1994 Jul;87(3):453-8 - PubMed
  42. J Immunol. 1994 Aug 15;153(4):1687-96 - PubMed
  43. Arch Pharm Res. 2009 May;32(5):781-7 - PubMed
  44. J Surg Res. 2011 Oct;170(2):e243-51 - PubMed
  45. Cancer Immunol Immunother. 2000 Aug;49(6):335-45 - PubMed
  46. Lancet. 2000 Sep 2;356(9232):802-7 - PubMed
  47. Leukemia. 1998 Dec;12(12):2029-33 - PubMed
  48. Blood. 2001 May 15;97(10):2923-31 - PubMed
  49. Arch Pharm Res. 2007 Nov;30(11):1464-70 - PubMed
  50. Biol Blood Marrow Transplant. 2001;7(4):216-22 - PubMed
  51. Cancer Immunol Immunother. 2010 Sep;59(9):1325-34 - PubMed
  52. Biol Blood Marrow Transplant. 2001;7(10):532-42 - PubMed
  53. Cytotherapy. 2012 Jan;14(1):91-103 - PubMed
  54. Pediatr Blood Cancer. 2008 Apr;50(4):739-45 - PubMed
  55. Int Immunopharmacol. 2007 Dec 15;7(13):1793-801 - PubMed
  56. Blood. 1998 Nov 1;92(9):3318-27 - PubMed
  57. Blood. 2005 Jan 1;105(1):241-50 - PubMed
  58. Cell Death Differ. 2003 Jun;10(6):729-39 - PubMed
  59. Ann Hematol. 2011 Aug;90(8):873-85 - PubMed
  60. Exp Hematol. 2003 Oct;31(10):897-902 - PubMed
  61. World J Gastroenterol. 2002 Jun;8(3):464-8 - PubMed
  62. Leukemia. 2005 Aug;19(8):1384-90 - PubMed
  63. Clin Cancer Res. 2000 Oct;6(10):4119-27 - PubMed

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