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CD47 antibody

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https://www.readbyqxmd.com/read/28977832/anti-cd47-antibodies-induce-phagocytosis-of-live-malignant-b-cells-by-macrophages-via-the-fc-domain-resulting-in-cell-death-by-phagoptosis
#1
Lucy E Métayer, Anna Vilalta, G A Amos Burke, Guy C Brown
When expressed on the surface of cells, CD47 inhibits phagocytosis of these cells by phagocytes. Most human cancers overexpress CD47, and antibodies to CD47 have shown a remarkable ability to clear a range of cancers in animal models. However, the mechanism by which these antibodies cause cancer cell death is unclear. We find that CD47 is expressed on the surface of three B-cell lines from human malignancies: 697 (pre-B-ALL lymphoblasts), Ramos and DG-75 (both mature B-cells, Burkitt's lymphoma), and anti-CD47 antibodies greatly increase the phagocytosis of all three cell line by macrophages...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975767/cd47-blockade-reduces-ischemia-reperfusion-injury-in-donation-after-cardiac-death-rat-kidney-transplantation
#2
Xuanchuan Wang, Min Xu, Jianluo Jia, Zhengyan Zhang, Joseph P Gaut, Gundumi A Upadhya, Pamela T Manning, Yiing Lin, William C Chapman
Modulation of nitric oxide (NO) activity through blockade of CD47 signaling has been shown to reduce ischemia-reperfusion injury (IRI) in various models of tissue ischemia. Here, we evaluate the potential effect of an antibody-mediated CD47 blockade in a syngeneic and an allogeneic DCD rat kidney transplant model. The donor organ was subjected to 1 hr of warm ischemia time after circulatory cessation, then flushed with a CD47 monoclonal antibody (CD47mAb) in the treatment group, or an isotype-matched immunoglobulin in the control group...
October 4, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28963754/diminished-presentation-of-complement-regulatory-protein-cd55-on-red-blood-cells-from-patients-with-hereditary-haemolytic-anaemias
#3
A Loniewska-Lwowska, K Koza, E Mendek-Czajkowska, P Wieszczy, A Adamowicz-Salach, K Branicka, I Witos, A Sapala-Smoczynska, T Jackowska, J Fabijanska-Mitek
INTRODUCTION: Hereditary haemolytic anaemias (HHA) encompass a heterogeneous group of anaemias characterized by decreased red blood cell survival. The aim of this study was to evaluate the status of red blood cell (RBC) surface molecules known or previously proposed to participate in preventing premature RBC clearance, analysing erythrocytes from patients with two types of HHA: hereditary spherocytosis (HS) and microcytosis. MATERIAL/METHODS: Relative binding of five monoclonal antibodies (mAbs), anti-CD55, anti-CD59, anti-CD44, anti-CD47 and anti-CD58, was evaluated in erythrocytes of patients with HS and hereditary microcytosis, using flow cytometry...
September 30, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28952147/genetic-variation-of-human-neutrophil-fc%C3%AE-receptors-and-sirp%C3%AE-in-antibody-dependent-cellular-cytotoxicity-towards-cancer-cells
#4
Louise W Treffers, Xi Wen Zhao, Joris van der Heijden, Sietse Q Nagelkerke, Dieke J van Rees, Patricia Gonzalez, Judy Geissler, Paul Verkuijlen, Michel van Houdt, Martin de Boer, Taco W Kuijpers, Timo K van den Berg, Hanke L Matlung
The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti-cancer antibodies act through different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47-SIRPα interactions, but the magnitude of this enhancement also varies among individuals. Both FcγR and SIRPα display considerable genetic variation, and we investigated whether this explains some of the variability in ADCC...
September 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28920097/acute-cd47-blockade-during-ischemic-myocardial-reperfusion-enhances-phagocytosis-associated-cardiac-repair
#5
Shuang Zhang, Xin-Yi Yeap, Matthew DeBerge, Nivedita K Naresh, Kevin Wang, Zhengxin Jiang, Jane E Wilcox, Steven M White, John P Morrow, Paul W Burridge, Daniel Procissi, Evan A Scott, William Frazier, Edward B Thorp
Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28874561/localized-cd47-blockade-enhances-immunotherapy-for-murine-melanoma
#6
Jessica R Ingram, Olga S Blomberg, Jonathan T Sockolosky, Lestat Ali, Florian I Schmidt, Novalia Pishesha, Camilo Espinosa, Stephanie K Dougan, K Christopher Garcia, Hidde L Ploegh, Michael Dougan
CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28870843/phosphatidylserine-a-cancer-cell-targeting-biomarker
#7
REVIEW
Bhupender Sharma, Shamsher S Kanwar
Cancer is a leading cause of mortality and morbidity globally. Many prominent cancer-associated molecules have been identified over the recent years which include EGFR, CD44, TGFbRII, HER2, miR-497, NMP22, BTA, Fibrin/FDP etc. These biomarkers are often used for screening, detection, diagnosis, prognosis, prediction and monitoring of cancer development. Phosphatidylserine (PS) is an essential component in all human cells which is present on the inner leaflet of the cell membrane. The oxidative stress causes exposure of PS on the surface of the vascular endothelium in the cancer cells (lung, breast, pancreatic, bladder, skin, brain metastasis, rectal adenocarcinoma etc...
September 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28745331/cd47-blockade-enhances-therapeutic-activity-of-tcr-mimic-antibodies-to-ultra-low-density-cancer-epitopes
#8
M D Mathias, J T Sockolosky, A Y Chang, K S Tan, C Liu, K C Garcia, D A Scheinberg
No abstract text is available yet for this article.
October 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28669759/sirpa-inhibited-marrow-derived-macrophages-engorge-accumulate-and-differentiate-in-antibody-targeted-regression-of-solid-tumors
#9
Cory M Alvey, Kyle R Spinler, Jerome Irianto, Charlotte R Pfeifer, Brandon Hayes, Yuntao Xia, Sangkyun Cho, P C P Dave Dingal, Jake Hsu, Lucas Smith, Manu Tewari, Dennis E Discher
Marrow-derived macrophages are highly phagocytic, but whether they can also traffic into solid tumors and engulf cancer cells is questionable, given the well-known limitations of tumor-associated macrophages (TAMs). Here, SIRPα on macrophages from mouse and human marrow was inhibited to block recognition of its ligand, the "marker of self" CD47 on all other cells. These macrophages were then systemically injected into mice with fluorescent human tumors that had been antibody targeted. Within days, the tumors regressed, and single-cell fluorescence analyses showed that the more the macrophages engulfed, the more they accumulated within regressing tumors...
July 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28644129/anti-cd47-antibodies-induce-phagocytosis-of-live-malignant-b-cells-by-macrophages-via-the-fc-domain-resulting-in-cell-death-by-phagoptosis
#10
Lucy E Métayer, Anna Vilalta, G A Amos Burke, Guy C Brown
When expressed on the surface of cells, CD47 inhibits phagocytosis of these cells by phagocytes. Most human cancers overexpress CD47, and antibodies to CD47 have shown a remarkable ability to clear a range of cancers in animal models. However, the mechanism by which these antibodies cause cancer cell death is unclear. We find that CD47 is expressed on the surface of three B-cell lines from human malignancies: 697 (pre-B-ALL lymphoblasts), Ramos and DG-75 (both mature B-cells, Burkitt's lymphoma), and anti-CD47 antibodies greatly increase the phagocytosis of all three cell line by macrophages...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537232/-cd47-receptor-as-a-primary-target-for-cancer-therapy
#11
REVIEW
N M Ratnikova, Y N Lezhnin, E I Frolova, J E Kravchenko, S P Chumakov
Recently, a number of new highly efficient antibody-based anticancer therapeutics have emerged. These receptor-binding antibodies have beneficial toxicity profiles associated with relatively mild side effects. Therefore, the search for novel surface proteins that are present on cancer cells and play important metabolic or defensive roles has intensified. Additionally, the therapeutic stimulation of patient's immune system in order to aim its components, specifically, phagocytes and cytotoxic T-lymphocytes, at tumor cells is gaining traction...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28484448/anti-cd47-antibody-as-a-targeted-therapeutic-agent-for-human-lung-cancer-and-cancer-stem-cells
#12
Liang Liu, Lin Zhang, Lin Yang, Hui Li, Runmei Li, Jinpu Yu, Lili Yang, Feng Wei, Cihui Yan, Qian Sun, Hua Zhao, Fan Yang, Hao Jin, Jian Wang, Shizhen Emily Wang, Xiubao Ren
Accumulating evidence indicates that a small subset of cancer cells, termed the tumor-initiating cells or cancer stem cells (CSCs), construct a reservoir of self-sustaining cancer cells with the characteristic ability to self-renew and maintain the tumor mass. The CSCs play an important role in the tumor initiation, development, relapse, metastasis, and the ineffectiveness of conventional cancer therapies. CD47 is a ligand for signal-regulatory protein-α expressed on phagocytic cells and functions to inhibit phagocytosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424250/unifying-mechanism-for-different-fibrotic-diseases
#13
Gerlinde Wernig, Shih-Yu Chen, Lu Cui, Camille Van Neste, Jonathan M Tsai, Neeraja Kambham, Hannes Vogel, Yaso Natkunam, D Gary Gilliland, Garry Nolan, Irving L Weissman
Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28398662/rhesus-ce-expression-on-patient-red-blood-cells-is-an-independent-prognostic-factor-for-adenocarcinoma-of-the-lung
#14
A B Schulze, L H Schmidt, L Baie, B Heitkötter, A Kümmel, M Mohr, R Buhl, H Hillmann, G Geißler, R Kelsch, D Görlich, W E Berdel, W Hartmann, R Wiewrodt
OBJECTIVES: The influence of blood group antigens on cancerogenesis is shown for distinct tumor types, yet the impact of Rhesus blood group antigens in lung cancer is not clarified. MATERIALS AND METHODS: To investigate the impact of Rhesus blood groups a non-small cell lung cancer (NSCLC) collective (n=1,047) was analyzed retrospectively. Using a second cohort of n=340 primarily operated stage I-III NSCLC patients, we evaluated immunohistochemistry of CD47-antibody stained tissue samples in correlation to histopathologic subtype and Rhesus blood group...
April 11, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28380460/cd47-promotes-ovarian-cancer-progression-by-inhibiting-macrophage-phagocytosis
#15
Ran Liu, Huiting Wei, Peng Gao, Hu Yu, Ke Wang, Zheng Fu, Baohui Ju, Meng Zhao, Shangwen Dong, Zhijun Li, Yifeng He, Yuting Huang, Zhi Yao
Targeting CD47 efficiently enhances macrophage phagocytosis in both physiological and pathological conditions. Anti-CD47 antibodies have been shown to inhibit the progression of several types of cancer. However, the mechanism of anti-CD47 monoclonal antibody (mAb) treatment remains controversial. In this study, we confirmed that CD47 protein is highly expressed in ovarian cancer, and is correlated with poor clinical characteristics and prognosis. CD47 knockdown in the ovarian cancer cell line, SK-OV-3, promoted phagocytosis by macrophages in vitro and inhibited tumor growth in vivo...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28361932/neuro-oncology-cd47-antibody-helps-phagocytes-fight-paediatric-cancer
#16
Charlotte Ridler
No abstract text is available yet for this article.
March 31, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28351890/targeting-cd47-and-autophagy-elicited-enhanced-antitumor-effects-in-non-small-cell-lung-cancer
#17
Xuyao Zhang, Jiajun Fan, Shaofei Wang, Yubin Li, Yichen Wang, Song Li, Jingyun Luan, Ziyu Wang, Ping Song, Qicheng Chen, Wenzhi Tian, Dianwen Ju
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in non-small cell lung cancer (NSCLC). SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28341665/an-anti-cd47-antibody-is-effective-in-pediatric-brain-tumor-models
#18
(no author information available yet)
The anti-CD47 antibody Hu5F9-G4 selectively kills tumor cells in pediatric brain tumor PDX models.
March 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28298418/disrupting-the-cd47-sirp%C3%AE-anti-phagocytic-axis-by-a-humanized-anti-cd47-antibody-is-an-efficacious-treatment-for-malignant-pediatric-brain-tumors
#19
Sharareh Gholamin, Siddhartha S Mitra, Abdullah H Feroze, Jie Liu, Suzana A Kahn, Michael Zhang, Rogelio Esparza, Chase Richard, Vijay Ramaswamy, Marc Remke, Anne K Volkmer, Stephen Willingham, Anitha Ponnuswami, Aaron McCarty, Patricia Lovelace, Theresa A Storm, Simone Schubert, Gregor Hutter, Cyndhavi Narayanan, Pauline Chu, Eric H Raabe, Griffith Harsh, Michael D Taylor, Michelle Monje, Yoon-Jae Cho, Ravi Majeti, Jens P Volkmer, Paul G Fisher, Gerald Grant, Gary K Steinberg, Hannes Vogel, Michael Edwards, Irving L Weissman, Samuel H Cheshier
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#20
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
May 2017: European Journal of Cancer
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