Cytokine induced killer (CIK) cells are in clinical testing against various tumor types including multiple myeloma. Here, 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 pre-treating the myeloma cells with ionizing radiation (XRT). KAS-6/1 cells were killed by co-culture with CIK or MV-infected CIK (CIK/MV) cells and addition of an anti-NKG2D antibody inhibited cytolysis by 50%. Human bone marrow stromal cells can however 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 to 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 to CIK/MV with no XRT. This study demonstrates the potential of CIK against myeloma and that combination of virotherapy with radiation could be used to further enhance therapeutic outcome using CIK cells.
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