Evaluation of the use of biochar to stabilize polycyclic aromatic hydrocarbons and phthalates in sediment.

Three types of biochar (BC) (mulberry biochar (MB), wheat straw biochar, and pine tree sawdust biochar) were prepared and used to stabilize hydrophobic organic compounds (HOCs) in contaminated sediment. The kinetics of HOC adsorption to the BCs had two distinct stages. The second stage adsorption process was longer for MB than the other BCs, presumably because MB contained large pores, mesopores, and micropores. The adsorption isotherms for the three BCs were described well by the Freundlich model. The adsorption capacities of MB, WS and PT for HOCs ranged between 106.7 and 1202 µg/g, 135.1 and 1002 µg/g, and 255.6 and 909 µg/g, respectively. The apparent HOC adsorption coefficients (KBC-w) for the three BCs were determined from the isotherm data and were similar. The HOC logKOW values correlated well with the logKBC-w values. In sediment slurry experiments, HOCs were much more effectively stabilized by MB than wheat straw and pine tree sawdust biochar. This was probably because of the MB pore characteristics that favored adsorption of HOCs of various molecular sizes. The Fourier-transform infrared and Raman spectra indicated that the main binding mechanisms were hydrogen boding, hydrophobic interactions, and π-π interactions. MB was found to be a possible agent for stabilizing HOCs in contaminated sediment. HOCs in sediment slurry continued to become adsorbed to MB for a long time, indicating that relatively long reaction times should be allowed for in situ remediation using MB.

Therapeutic effiacy of T cells expressing chimeric antigen receptor derived from a mesothelin-specific scFv in orthotopic human pancreatic cancer animal models.

Novel CAR T cells targeting mesothelin (MSLN) expressed on pancreatic cancer cells were developed to overcome the limit of the clinical efficacy of CAR T cell therapy for pancreatic cancer patients. Optimal single-chain variable fragments (scFv) binding to MSLN were selected based on the binding activity and the functional effectiveness of various scFv containing CAR-expressing T cells. Engineered MSLN CAR T cells showed successful anti-tumor activity specific to MSLN expression level. Furthermore, MSLN CAR T cells were evaluated for the anti-cancer efficacy in orthotopic mouse models bearing pancreatic cancer cells, MIA Paca-2, MSLN-overexpressed MIA Paca-2 or endogenously MSLN-expressing AsPC-1. Mice were randomized into control, mock treated, MS501 BBz treated, MS501 28z treated or MS501 28BBz treated group. Mice were monitored by weekly IVIS imaging and tumors were harvested and analyzed by immunohistochemical analyses. MSLN CAR T cells produced the therapeutic effect in orthotopic animal models with complete remission in significant number of mice. Histopathological analysis indicated that CD4+ and CD8+ MSLN CAR T cells infiltrated pancreatic tumor tissue and led to cancer cell eradication. Our results demonstrated the anti-tumor efficacy of MSLN CAR T cell therapy against pancreatic cancer, suggesting its therapeutic potential.

Natural killer cells as a promising therapeutic target for cancer immunotherapy.

Natural killer (NK) cells are innate lymphoid cells that provide early protection against cancer development via their selectivity to kill abnormal cells undergoing cellular transformation without the need for prior stimulation. Given the correlation between NK cell dysfunction and cancer prognosis, restoration of endogenous NK cells in the tumor microenvironment or adoptive transfer of NK cells with improved function holds great promise in cancer treatment. Furthermore, MHC-unrestricted tumor lysis by NK cells complements the MHC-restricted killing of tumor cells by cytotoxic T cells, thus positioning NK cells as an alternative or complementary therapeutic target for cancers that are refractory to T cell-based therapy. Although previous therapeutic strategies have focused on the manipulation of NK cell inhibitory receptors, recent advances in our understanding of NK cell activation have provided additional promising strategies to enhance NK cell reactivity against cancer. These approaches include targeting immunosuppressive mechanisms in the tumor microenvironment, such as immune checkpoint receptors, and further enhancing NK cell activation via modulation of intracellular checkpoint molecules or incorporation of tumor-directed chimeric antigen receptors. Thus, an in-depth understanding of NK cell activation will facilitate the optimal design of therapeutic strategies against refractory cancers, possibly in rational and synergistic combination with other therapies.

Progressive Impairment of NK Cell Cytotoxic Degranulation Is Associated With TGF-ß1 Deregulation and Disease Progression in Pancreatic Cancer.

Natural killer (NK) cells are key effectors in cancer immunosurveillance and can be used as a prognostic biomarker in diverse cancers. Nonetheless, the role of NK cells in pancreatic cancer (PC) remains elusive, given conflicting data on their association with disease prognosis. In this study, using conventional K562 target cells and complementary engineered target cells providing defined and synergistic stimulation for NK cell activation, a correlation between impaired NK cell cytotoxic degranulation and PC progression was determined. Peripheral blood mononuclear cells (PBMCs) from 31 patients with newly diagnosed PC, 24 patients with non-malignant tumors, and 37 healthy controls were analyzed by flow cytometry. The frequency, phenotype, and effector functions of the NK cells were evaluated, and correlations between NK cell functions and disease stage and prognosis were analyzed. The results demonstrated that effector functions, but not frequency, of NK cells was progressively decreased on a per-cell basis during PC progression. Impaired cytotoxic degranulation, but not IFN-γ production, was associated with clinical features indicating disease progression, such as high serum CA19-9 and high-grade tumors. Significantly, this impairment correlated with cancer recurrence and mortality in a prospective analysis. Furthermore, the impaired cytotoxic degranulation was unrelated to NKG2D downregulation but was associated with increased circulating and tumor-associated TGF-ß1 expression. Thus, NK cell cytotoxic activity was associated with PC progression and may be a favorable biomarker with predictive and prognostic value in PC.