Search results for " cytotoxic"
showing 10 items of 315 documents
A New 1D Ni (II) Coordination Polymer of s-Triazine Type Ligand and Thiocyanate as Linker via Unexpected Hydrolysis of 2,4-Bis(3,5-dimethyl-1H-pyrazo…
2023
A new 1D Ni(II) coordination polymer was synthesized by the reaction of NiSO4·6H2O with 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (BPT) and SCN− as a linker in an acidic medium by heating under reflux conditions. Unusually, the BPT ligand underwent acid-mediated hydrolysis by losing one of the pyrazolyl arms afforded the polymeric [Ni(MPT)(H2O)(SCN)2]n complex (MPT: 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazin-2-ol. The Ni(II) center is coordinated with one MPT as a bidentate NN-chelate, one water molecule, and two thiocyanate groups in cis positions to one another. One of the thiocyanate groups acts as a bridging ligand between metal centers, l…
Superior antitumor in vitro responses of allogeneic matched sibling compared with autologous patient CD8+ T cells.
2006
AbstractAllogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8+ T cells, whereas CD4+ T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor …
IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)
1993
Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigenic challenge, may also influence frequencies of circulating antigen-specific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with n…
Functionally Active T Cell Receptor/CD3 Complexes Are Present at the Surface of Cloned Cytotoxic T Cells without Fluorescence-Immunological Detectabi…
1996
The cytotoxic T cell clone 10BK.1 is activated in response to the ovalbumin peptide OVA257-264 in a major histocompatibility complex class I-restricted manner. Following activation 10BK.1 cells proliferate, secrete lymphokines, and kill syn- and allogeneic target cells. Using immunofluorescence analysis we detected CD8, LFA-1, and ICAM-1 on the surface of 10BK.1 cells, but no CD3 or T cell receptor (TCR). In contrast, the proliferative response of 10BK.1 cells to antigen was efficiently blocked by soluble antibodies directed at CD3 epsilon or TCR alpha beta, but not by antibodies directed at TCR gamma delta. In addition, lysis of target cells was blocked by F(ab')2 fragments of antibodies d…
An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated an…
2009
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. alpha-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to alpha-enolase. The present work was intended to assess the ability of alpha-enolase to induce antigen-specific T cell responses. We show that alpha-enolase-pulsed dendritic cells (DC) specifically stimulate healt…
Optimizing tumor-reactive γδ T cells for antibody-based cancer immunotherapy.
2010
Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu(+) breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent functi…
Effects of nordihydroguaiaretic acid on murine antibody-dependent cellular cytotoxicity.
1996
The purpose of this study was to analyze the effects of nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid, on antibody-dependent cellular cytotoxicity. Antibody-dependent cellular cytotoxicity mediated by murine spleen cells was significantly inhibited by concentrations of nordihydroguaiaretic acid from 10(-5) to 10(-4) M (1C50 = 2 x 10(-5) M). The inhibitory effect of nordihydroguaiaretic acid was also observed on antibody-dependent cellular cytotoxicity mediated by macrophage-depleted spleen cells as well as isolated macrophages. Nordihydroguaiaretic acid was highly effective when added at the beginning of the assay and was always present throughout t…
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
2008
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engag…
Global Functional Analyses of Cellular Responses to Pore-Forming Toxins
2011
Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we pe…
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner.
2007
Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, redu…