Inhibiting quorum sensing pathways to mitigate seawater desalination RO membrane biofouling

Bacterial biofilm formation, the main cause of membrane biofouling, is a crucial issue for membrane separation. Biofilm production is regulated by quorum sensing (QS) systems where bacteria secrete auto-inducers to communicate with neighboring bacteria. This research identified that several marine bacteria isolated from a desalination plant produced a low molecular weight auto-inducer 1 (AI-1) signaling molecule. AI-1 production in the mixed culture of the four different biofilm-forming marine bacteria was greater than in individual bacterial cultures. The QS inhibiting compounds, vanillin and cinnamaldehyde at 1200. mg/L significantly reduced biofilm formed by these marine bacteria by more than 79% and 70%, respectively in a microtiter plate assay. Anti-biofilm capabilities of vanillin and cinnamaldehyde were further assessed in a reverse osmosis membrane bio-monitoring system using mixed bacterial cultures and native uncultured bacterial communities in natural seawater. Confocal microscopy showed vanillin (1200. mg/L) significantly reduced biofilm extracellular polysaccharides and dead cells on the membrane surface (>. 40%, >. 20%). These results indicate that QS inhibitors have the potential to remediate membrane biofouling

Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy.

Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. Assessments were performed using in vitro myeloid or natural killer (NK) cell differentiation of human HSPCs transduced with lentiviral vectors carrying first and second generations of CD19-specific CAR. Gene transfer did not impair hematopoietic differentiation and cell proliferation when transduced at 1-2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive cells, with second-generation CAR including CD28 domains being more efficient in NK cells. Our results provide evidence for the feasibility and efficacy of the modification of HSPC with CAR as a strategy for generating multiple lineages of effector cells for immunotherapy against B-lineage malignancies to augment graft-versus-leukemia activity

Modification of Hematopoietic Stem/Progenitor Cells with CD19-Specific Chimeric Antigen Receptors as a Novel Approach for Cancer Immunotherapy

Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. Assessments were performed using in vitro myeloid or natural killer (NK) cell differentiation of human HSPCs transduced with lentiviral vectors carrying first and second generations of CD19-specific CAR. Gene transfer did not impair hematopoietic differentiation and cell proliferation when transduced at 1–2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive cells, with second-generation CAR including CD28 domains being more efficient in NK cells. Our results provide evidence for the feasibility and efficacy of the modification of HSPC with CAR as a strategy for generating multiple lineages of effector cells for immunotherapy against B-lineage malignancies to augment graft-versus-leukemia activity