Search results for "macrophage"
showing 10 items of 781 documents
Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherap…
2015
The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluate…
Nanofitins targeting heat shock protein 110: an innovative immunotherapeutic modality in cancer.
2021
The presence of an inactivating heat shock protein 110 (HSP110) mutation in colorectal cancers has been correlated with an excellent prognosis and with the ability of HSP110 to favor the formation of tolerogenic (M2-like) macrophages. These clinical and experimental results suggest a potentially powerful new strategy against colorectal cancer: the inhibition of HSP110. In this work, as an alternative to neutralizing antibodies, Nanofitins (scaffold ~7 kDa proteins) targeting HSP110 were isolated from the screening of a synthetic Nanofitin library, and their capacity to bind (immunoprecipitation, biolayer interferometry) and to inhibit HSP110 was analyzed in vitro and in vivo. Three Nanofiti…
Tumor and its microenvironment: a synergistic interplay.
2013
The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species …
Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?
2002
alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant V alpha 14 J alpha 281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. …
CD83+ human dendritic cells transfected with tumor peptide cDNA by electroporation induce specific T-cell responses: A potential tool for gene immuno…
2000
Dendritic cells (DC) are the most potent immunostimulatory cells, with the capacity to induce primary T-cell responses. Functional autologous DC can be generated from fetal calf serum-free peripheral blood mononuclear cells in the presence of interleukin-4 and granulocyte-macrophage colony-stimulating factor and are stimulated with a defined cytokine cocktail for terminal maturation. We were able to establish a nonviral transfection protocol for these DC by electroporation. Using enhanced green fluorescent protein as a reporter gene, we achieved transfection efficiencies of up to 10%. FACScan analyses revealed a stable phenotype, and the expression of major histocompatibility complex class …
Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.
2013
Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In prevent…
Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer
2022
The role of the tumor microenvironment (TME) in the progression of colorectal cancer (CRC) and its acquisition of resistance to treatment become the research hotspots. As an important component of TME, the tumor-associated macrophages (TAMs) regulate multiple critical oncogenic processes, namely, occurrence, proliferation, metastasis, and drug resistance in CRC. In this review, we have discussed the functional and therapeutic significance of TAMs in CRC. M1 macrophages act as the tumor suppressor while M2 macrophages promote CRC. The polarization of TAMs is mainly regulated by the pathways such as NFKB1 pathways, STAT3 pathways, WNT5A pathways, and PI3K pathways in CRC. Furthermore, the M2 …
Drying enhances immunoactivity of spent brewer's yeast cell wall β-D-glucans.
2015
Due to immunological activity, microbial cell wall polysaccharides are defined as 'biological response modifiers' (BRM). Cell walls of spent brewer's yeast also have some BRM activity. However, up to date there is no consensus on the use of spent brewer's yeast D-glucan as specific BRM in humans or animals. The aim of this paper is to demonstrate the potential of spent brewer's yeast β-D-glucans as BRM, and drying as an efficient pretreatment to increase β-D-glucan's immunogenic activity. Our results revealed that drying does not change spent brewer's yeast biomass carbohydrate content as well as the chemical structure of purified β-D-glucan. However, drying increased purified β-D-glucan TN…
Altered expression of inflammation-related genes in human carotid atherosclerotic plaques.
2011
Abstract Objective Inflammation is a pivotal process in atherosclerosis development and progression, but the underlying molecular mechanisms remain largely obscure. We have conducted an extensive expression study of atherosclerotic plaques to identify the inflammatory pathways involved in atherosclerosis. Methods We studied 11 human carotid plaques, their respective adjacent regions and 7 control arteries from different subjects. Expression of 92 genes was studied by TaqMan low-density array human inflammation panel. Human aortic endothelial and smooth muscle cells were used for in vitro experiments. Results The mRNA levels of 44/92 genes (48%) differed significantly between the tissues exa…
Expression patterns of complex glycoconjugates and endogenous lectins during fetal development of the viscerocranium
1999
Summary Experimental evidence suggests that carbohydrates and their corresponding receptors (endogenous lectins) decode biological information. Therefore, the expression of complex oligosaccharides — the potential ligand part of this recognition system — during chondrogenesis and osteogenesis was determined in the viscerocranium of fetal rats by mapping the staining patterns of exogenous lectins. Results were compared with the expression of bone- and/or cartilage-specific core proteins and the binding profiles of neoglycoconjugates. These synthetic tools make possible the localization of sugar-ligand-binding sites. The spatial and temporal distribution patterns of glycoconjugates were highl…