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. 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.

Increase of CIK cell efficacy by upregulating cell surface MICA and inhibition of NKG2D ligand shedding in multiple myeloma

“…This result confirms previous reports stating that a selected combination of histone deacetylase inhibitors, matrix metalloproteinase inhibitors, or PAO prior to immune cell therapy can improve the efficiency of immune cells in targeting tumors . In support of available literature, it also proves the cytotoxic potential of CIK cells in targeting MM.…”

Immunomodulatory Effects of Radiation: What is Next for Cancer Therapy?

“…The stress ligands MICA/B can bind to cognate receptors (NKG2D) on cytokine-inducible lymphocytes, NK cells and T cells causing activation of these cells [24]. Liu et al irradiated human myeloma cells (KAS-6/1) at various doses and analyzed the cells for expression of MICA/B 24 h postirradiation [25]. A dose-dependent increase in both MICA/B expression at doses as low as 2 Gy was observed.…”

Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer

“…CIK cells exhibit strong antitumor activity and non-major histocompatibility complex-restricted tumor-killing characteristics (10,20). A number of studies suggest that CIK cells co-cultured with DCs exhibit stronger tumoricidal effects and have already produced better results in different tumor types (21,22). CIK cells have cytotoxic properties and are able to kill tumor cells directly as well as indirectly, through stimulation of the host immune system.…”