TY - JOUR
T1 - Enhancing cytokine-induced killer cell therapy of multiple myeloma
AU - Liu, Chunsheng
AU - Suksanpaisan, Lukkana
AU - Chen, Yun Wen
AU - Russell, Stephen J.
AU - Peng, Kah Whye
N1 - Funding Information:
This study was supported by grants from the National Institutes of Health–National Cancer Institute ( CA129193 , CA129966 , CA136547 , Mayo Clinic SPORE in Ovarian Cancer P50CA136393 ). We thank Dr. Allan B Dietz (Mayo Clinic Human Cell Therapy Laboratory) for providing the CD3-sorted T cells.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84878200376&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878200376&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2013.01.010
DO - 10.1016/j.exphem.2013.01.010
M3 - Article
C2 - 23403007
AN - SCOPUS:84878200376
SN - 0301-472X
VL - 41
SP - 508
EP - 517
JO - Experimental Hematology
JF - Experimental Hematology
IS - 6
ER -