title: Enhancing cytokine-induced killer cell therapy of multiple myeloma.
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.
authors: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors: Chunsheng
authors: C
authors: Liu
authors: Lukkana
authors: L
authors: Suksanpaisan
authors: Yun-Wen
authors: YW
authors: Chen
authors: Stephen J
authors: SJ
authors: Russell
authors: Kah-Whye
authors: KW
authors: Peng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000276:immunology / Q000637:transplantation / Q000821:virology; D018920:Coculture Techniques; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive; D008459:Measles virus / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D050130:Oncolytic Virotherapy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D017154:Stromal Cells / Q000637:transplantation; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger
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