Search results for "phage"
showing 10 items of 1573 documents
CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphoc…
2009
AbstractCD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors…
Margetuximab (M) combined with anti-PD-1 (retifanlimab) or anti-PD-1/LAG-3 (tebotelimab) +/- chemotherapy (CTX) in first-line therapy of advanced/met…
2021
TPS264 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care 1st-line therapy for advanced HER2+ GEJ/GC patients. M, an investigational Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. Data suggest margetuximab coordinately enhances both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. Retifanlimab (also known as MGA012 or INCMGA00012) is a humanized, hinge-stabilized, IgG4 Κ anti-PD-1 mAb blocking binding of PD-L1 …
A new assay for O6-alkylguanine-DNA-alkyltransferase to determine DNA repair capacities using lambda-phage DNA as substrate.
1990
One O6-methylguanine (O6-meG) was introduced into each BamHI site of lambda-phage DNA as a substrate for the determination of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase. A new assay using as the detection group 32P-labeled phosphate introduced at the 3' position of the modified nucleoside by incorporation of 32P-labeled TTP in the 3'-neighboring position proved highly sensitive: 10(-16) mol of the DNA lesion was still easily detectable. This DNA, which has greater than 1000 bp represents a good model for cellular DNA and was used as a substrate to measure the individual repair capacities for O6-meG in human lymphocytes of 20 healthy male and female donors. There were great …
Abstract 1631: GPR65 is a critical mediator of low pH induced immunosuppressive signalling in tumor associated macrophages: Human target validation o…
2021
Abstract Tumor-associated macrophages (TAMs) are the major innate immune component in the microenvironment of solid tumors. These cells are highly heterogeneous and plastic but often display a pronounced immunosuppressive phenotype that supports primary tumor growth and metastasis. A recently identified determinant of the immunosuppressive properties of TAMs is the activation of the pH-sensing G protein-coupled receptor, GPR65, on these cells by the acidic microenvironment that is inherent to many advanced solid tumours1. Previous work in mouse macrophages has shown that GPR65 activation leads to an elevation of inducible cAMP early repressor (ICER), an isoform of the CREM gene, which in tu…
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…
Confocal laser endoscopy: new approach to the early diagnosis of tumors of the esophagus and stomach
2006
The prognosis of malignancies of the upper gastrointestinal tract is poor if early diagnosis is missed. Therefore, a rapid in vivo diagnosis of early cancer and premalignant lesions is highly important for succesful therapy. Confocal laser endomicroscopy allows in vivo cellular and subcellular imaging at high resolutions during ongoing endoscopy. The first studies and clinical observations suggest a major role of this novel technique in the in vivo diagnosis of cancer of the esophagus and stomach and of precursor conditions, such as Barrett’s esophagus, intestinal metaplasia of the stomach and Helicobacter pylori infection. Based on recent experiences from animal models, future studies wil…
Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.
2008
This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expressi…
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. …