Enhancing cytokine-induced killer cell therapy of multiple myeloma

Chunsheng Liu, Lukkana Suksanpaisan, Yun-Wen Chen, Stephen J. Russell, Kah Whye Peng

Research output: Contribution to journalArticle

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Abstract

Cytokine-induced killer (CIK) cells are in clinical testing against various tumor types, including multiple myeloma. In this study, we show that CIK cells have activity against subcutaneous and disseminated models of human myeloma (KAS-6/1), which can be enhanced by infecting the CIK cells with an oncolytic measles virus (MV) or by pretreating the myeloma cells with ionizing radiation (XRT). KAS-6/1 cells were killed by coculture with CIK or MV-infected CIK (CIK/MV) cells, and the addition of an anti-NKG2D antibody inhibited cytolysis by 50%. However, human bone marrow stromal cells can reduce CIK and CIK/MV mediated killing of myeloma cells (RPMI 8226, JJN-3 and MM1). In vivo, CIK and CIK/MV prolonged the survival of mice with systemic myeloma, although CIK/MV showed enhanced antitumor activity compared with CIK. Irradiation of the KAS-6/1 cells induced mRNA and protein expression of NKG2D ligands, MICA, and MICB in a dose-dependent manner and enhanced delivery of CIK/MV to the irradiated tumors. In both subcutaneous and disseminated myeloma models, XRT at 2 Gy resulted in superior prolongation of the survival of mice given CIK/MV therapy compared with CIK/MV with no XRT. This study demonstrates the potential of CIK against myeloma and that the combination of virotherapy with radiation could be used to further enhance therapeutic outcome using CIK cells.

Original languageEnglish
Pages (from-to)508-517
Number of pages10
JournalExperimental Hematology
Volume41
Issue number6
DOIs
Publication statusPublished - 2013 Jun 1

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Cytokine-Induced Killer Cells
Cell- and Tissue-Based Therapy
Multiple Myeloma
Measles virus
Cytokines
Oncolytic Viruses
Coculture Techniques
Ionizing Radiation

All Science Journal Classification (ASJC) codes

  • Hematology
  • Molecular Biology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Liu, Chunsheng ; Suksanpaisan, Lukkana ; Chen, Yun-Wen ; Russell, Stephen J. ; Peng, Kah Whye. / Enhancing cytokine-induced killer cell therapy of multiple myeloma. In: Experimental Hematology. 2013 ; Vol. 41, No. 6. pp. 508-517.
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Enhancing cytokine-induced killer cell therapy of multiple myeloma. / Liu, Chunsheng; Suksanpaisan, Lukkana; Chen, Yun-Wen; Russell, Stephen J.; Peng, Kah Whye.

In: Experimental Hematology, Vol. 41, No. 6, 01.06.2013, p. 508-517.

Research output: Contribution to journalArticle

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AB - Cytokine-induced killer (CIK) cells are in clinical testing against various tumor types, including multiple myeloma. In this study, we show that CIK cells have activity against subcutaneous and disseminated models of human myeloma (KAS-6/1), which can be enhanced by infecting the CIK cells with an oncolytic measles virus (MV) or by pretreating the myeloma cells with ionizing radiation (XRT). KAS-6/1 cells were killed by coculture with CIK or MV-infected CIK (CIK/MV) cells, and the addition of an anti-NKG2D antibody inhibited cytolysis by 50%. However, human bone marrow stromal cells can reduce CIK and CIK/MV mediated killing of myeloma cells (RPMI 8226, JJN-3 and MM1). In vivo, CIK and CIK/MV prolonged the survival of mice with systemic myeloma, although CIK/MV showed enhanced antitumor activity compared with CIK. Irradiation of the KAS-6/1 cells induced mRNA and protein expression of NKG2D ligands, MICA, and MICB in a dose-dependent manner and enhanced delivery of CIK/MV to the irradiated tumors. In both subcutaneous and disseminated myeloma models, XRT at 2 Gy resulted in superior prolongation of the survival of mice given CIK/MV therapy compared with CIK/MV with no XRT. This study demonstrates the potential of CIK against myeloma and that the combination of virotherapy with radiation could be used to further enhance therapeutic outcome using CIK cells.

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