Potent anti-myeloma efficacy of dendritic cell therapy in combination with pomalidomide and programmed death-ligand 1 blockade in a preclinical model of multiple myeloma.

Dendritic cell (DC)-based vaccines are recognized as a promising immunotherapeutic strategy against cancer; however, the efficacy of immunotherapy with DCs is controlled via immune checkpoints, such as programmed death-ligand 1 (PD-L1). PD-L1 expressed on DC and tumor cells binds to programmed death-1 (PD-1) receptors on the activated T cells, which leads to the inhibition of cytotoxic T cells. Blocking of PD-L1 on DC may lead to improve the efficacy of DC therapy for cancer.

Cellular immunotherapy in multiple myeloma.

In multiple myeloma (MM), the impaired function of several types of immune cells favors the tumor's escape from immune surveillance and, therefore, its growth and survival. Tremendous improvements have been made in the treatment of MM over the past decade but cellular immunotherapy using dendritic cells, natural killer cells, and genetically engineered T-cells represent a new therapeutic era. The application of these treatments is growing rapidly, based on their capacity to eradicate MM.

Synergistic Antimyeloma Activity of Dendritic Cells and Pomalidomide in a Murine Myeloma Model.

We have previously shown that immunization with tumor antigen-loaded dendritic cells (DCs) and the immunomodulating drug, lenalidomide, synergistically potentiates the enhancing antitumor immunity in a myeloma mouse model. In this study, we investigated the immunogenicity of DCs combined with pomalidomide and dexamethasone in a myeloma mouse model. MOPC-315 cells were injected subcutaneously to establish myeloma-bearing mice.

Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma.

The therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination with lenalidomide and programmed death (PD)-1 blockade in a model of murine myeloma. MOPC-315 cell lines were injected subcutaneously to establish myeloma-bearing mice and the following five test groups were established: PBS control, DCs, DCs + lenalidomide, DCs + PD-1 blockade, and DCs + lenalidomide + PD-1 blockade.

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia.

We investigated the effects of an Na(+)/H(+) exchanger inhibitor, sabiporide, on excitotoxicity in cultured neuronal cells and in vivo. Sabiporide attenuated glutamate- or NMDA (N-methyl-d-aspartic acid)-induced neuronal cell death. Sabiporide also reduced glutamate or NMDA-induced increase in [Ca(2+)](i).

Activation of protein kinase C-delta attenuates kainate-induced cell death of cortical neurons.

We investigated the role of individual protein kinase C (PKC) isoforms during kainate toxicity in cortical neurons. Treatment with 50 microM kainate induced isoform-specific activation of PKC-delta according to the translocation from the soluble to the particulate fraction, while it caused remarkable decreases in PKC alpha, beta, epsilon and zeta in both fractions. Kainate-induced neuronal death was significantly increased by pharmacological inhibition of PKC-delta with rottlerin, suggesting a protective role of PKC-delta against kainate toxicity.

N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells (bEnd.3).

In this study, we investigated whether carbofuran, a commonly used carbamate pesticide, and N-nitrosocarbofuran (NOCF), the N-nitroso metabolite of carbofuran, have cytotoxicity in mouse brain microvascular endothelial cells (bEnd.3). Results from the MTT assay in bEnd.