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CD47 antibody

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https://www.readbyqxmd.com/read/29864508/a-novel-fully-human-anti-cd47-antibody-as-a-potential-therapy-for-human-neoplasms-with-good-safety
#1
Xiao-Yan Yu, Wei-Yi Qiu, Feng Long, Xiao-Peng Yang, Chang Zhang, Lei Xu, Hong-Yan Chang, Peng Du, Xiao-Juan Hou, Yun-Zhou Yu, Da-di Zeng, Shuang Wang, Zhi-Wei Sun
Strategies for targeting CD47 are becoming a hot spot of cancer immunotherapy. However the ubiquitous expression of CD47, especially on the RBC, makes the targeted therapy facing safety risk issues. So, how to balance the safety and efficacy during CD47 inhibition is currently a major question. We had reported an anti-CD47 antibody ZF1 with potent anti-tumor effect. In this study, we further developed and assessed a novel fully human anti-CD47 antibody, AMMS4-G4, derived from ZF1 using affinity maturation. AMMS4-G4 exhibited equivalent anticancer effects with Hu5F9-G4, a humanized anti-CD47 antibody in clinical trial, on the potential of inducing significant phagocytosis of tumor cells in vitro and prolonging the survival of leukemia xenografted mice...
June 1, 2018: Biochimie
https://www.readbyqxmd.com/read/29805639/cd47-as-a-potential-prognostic-marker-for-oral-leukoplakia-and-oral-squamous-cell-carcinoma
#2
Xiaojing Ye, Xiaojun Wang, Rui Lu, Jing Zhang, Xinming Chen, Gang Zhou
Cluster of differentiation (CD)47, which acts as a negative indicator for phagocytic cells, is overexpressed on the surface of multiple human solid tumor cell types. Avoiding phagocytosis by CD47 is required for the progression of solid tumors. The present study investigated the expression of CD47 in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and preliminarily explored the impact of CD47 on the proliferation of OSCC cells. A total of 56 tissue samples, including 36 cases of OLK, 10 cases of OSCC and 10 cases of normal oral mucosa (NOM) were selected to detect the expression of CD47 by immunohistochemistry...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29765073/oncotically-driven-control-over-glycocalyx-dimension-for-cell-surface-engineering-and-protein-binding-in-the-longitudinal-direction
#3
Erika M J Siren, Rafi Chapanian, Iren Constantinescu, Donald E Brooks, Jayachandran N Kizhakkedathu
Here we present a simple technique for re-directing reactions on the cell surface to the outermost region of the glycocalyx. Macromolecular crowding with inert polymers was utilized to reversibly alter the accessibility of glycocalyx proteoglycans toward cell-surface reactive probes allowing for reactivity control in the longitudinal direction ('z'-direction) on the glycocalyx. Studies in HUVECs demonstrated an oncotically driven collapse of the glycocalyx brush structure in the presence of crowders as the mechanism responsible for re-directing reactivity...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29755958/gut-microbiota-contributes-to-resistance-against-pneumococcal-pneumonia-in-immunodeficient-rag-mice
#4
Krysta M Felix, Ivan A Jaimez, Thuy-Vi V Nguyen, Heqing Ma, Walid A Raslan, Christina N Klinger, Kristian P Doyle, Hsin-Jung J Wu
Streptococcus pneumoniae causes infection-related mortality worldwide. Immunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable, yet little is known regarding S. pneumoniae- related pathogenesis and protection in immunocompromised hosts. Recently, strong interest has emerged in the gut microbiota's impact on lung diseases, or the "gut-lung axis." However, the mechanisms of gut microbiota protection against gut-distal lung diseases like pneumonia remain unclear...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29748606/cd47-ligation-induced-cell-death-in-t-acute-lymphoblastic-leukemia
#5
Pascal Leclair, Chi-Chao Liu, Mahdis Monajemi, Gregor S Reid, Laura M Sly, Chinten James Lim
CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#6
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29709247/blocking-don-t-eat-me-signal-of-cd47-sirp%C3%AE-in-hematological-malignancies-an-in-depth-review
#7
REVIEW
Atlantis Russ, Anh B Hua, William R Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S Carew, Steffan T Nawrocki, Daniel Persky, Faiz Anwer
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148...
April 14, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29600425/a-novel-bispecific-antibody-fusion-protein-co-targeting-egfr-and-cd47-with-enhanced-therapeutic-index
#8
Yun Yang, Rui Guo, Qi Chen, Youxun Liu, Pengfei Zhang, Ziheng Zhang, Xi Chen, Tianyun Wang
OBJECTIVE: To promote targeting specificity of anti-CD47 agents, we have constructed a novel bispecific antibody fusion protein against EGFR and CD47, which may minimize the "off-target" effects caused by CD47 expression on red blood cells. RESULTS: The novel bispecific antibody fusion protein, denoted as Bi-SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis-stimulation effects in vitro. Bi-SP treatment with a low dose more effectively inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRPα variant-Fc (SIRPαV-Fc) in the A431 xenograft tumor model...
May 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29473266/anti-human-sirp%C3%AE-antibody-is-a-new-tool-for-cancer-immunotherapy
#9
Yoji Murata, Daisuke Tanaka, Daisuke Hazama, Tadahiko Yanagita, Yasuyuki Saito, Takenori Kotani, Per-Arne Oldenborg, Takashi Matozaki
Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice...
February 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29416092/cd63-mhc-class-1-and-cd47-identify-subsets-of-extracellular-vesicles-containing-distinct-populations-of-noncoding-rnas
#10
Sukhbir Kaur, Abdel G Elkahloun, Anush Arakelyan, Lynn Young, Timothy G Myers, Francisco Otaizo-Carrasquero, Weiwei Wu, Leonid Margolis, David D Roberts
Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies...
February 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29399202/characterization-of-cluster-of-differentiation-47-expression-and-its-potential-as-a-therapeutic-target-in-esophageal-squamous-cell-cancer
#11
Chun-Lin Zhao, Shuang Yu, Shu-Hui Wang, Shi-Gang Li, Zhi-Ju Wang, Sheng-Na Han
The increased expression of cluster of differentiation (CD)47 has been identified in a number of different tumor types and is recognized as an adverse prognostic factor that indicates an increased risk of mortality in patients. The binding of CD47 to signal regulatory protein α (SIRPα) inhibits the macrophage phagocytosis of tumor cells by triggering an inhibitory 'do not eat me' signal. This is one of the mechanisms used by tumor cells to evade immune surveillance. In the present study, CD47 levels and macrophage infiltration were assessed in patients with esophageal squamous cell cancer (ESCC)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29338788/high-throughput-immunophenotypic-characterization-of-bone-marrow-and-cord-blood-derived-mesenchymal-stromal-cells-reveals-common-and-differentially-expressed-markers-identification-of-angiotensin-converting-enzyme-cd143-as-a-marker-differentially-expressed
#12
Eliana Amati, Omar Perbellini, Gianluca Rotta, Martina Bernardi, Katia Chieregato, Sabrina Sella, Francesco Rodeghiero, Marco Ruggeri, Giuseppe Astori
BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking...
January 16, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29296731/human-and-murine-splenic-neutrophils-are-potent-phagocytes-of-igg-opsonized-red-blood-cells
#13
Sanne M Meinderts, Per-Arne Oldenborg, Boukje M Beuger, Thomas R L Klei, Johanna Johansson, Taco W Kuijpers, Takashi Matozaki, Elise J Huisman, Masja de Haas, Timo K van den Berg, Robin van Bruggen
Red blood cell (RBC) clearance is known to occur primarily in the spleen, and is presumed to be executed by red pulp macrophages. Erythrophagocytosis in the spleen takes place as part of the homeostatic turnover of RBCs to remove old RBCs. It can be strongly promoted by immunoglobulin G (IgG) opsonization of RBCs, a condition that can occur as a consequence of autoantibody or alloantibody formation. The purpose of our study was to investigate which phagocytes are involved in IgG-mediated RBC clearance in the human spleen...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288236/cd47-blockade-as-an-adjuvant-immunotherapy-for-resectable-pancreatic-cancer
#14
Alex D Michaels, Timothy E Newhook, Sara J Adair, Sho Morioka, Bernadette J Goudreau, Sarbajeet Nagdas, Matthew G Mullen, Jesse B Persily, Timothy N J Bullock, Craig L Slingluff, Kodi S Ravichandran, J Thomas Parsons, Todd W Bauer
Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and adjuvant chemotherapy have an expected survival of only 2 years due to disease recurrence, frequently in the liver. We investigated the role of liver macrophages in progression of PDAC micrometastases to identify adjuvant treatment strategies that could prolong survival. Experimental Design: A murine splenic injection model of hepatic micrometastatic PDAC was used with five patient-derived PDAC tumors. The impact of liver macrophages on tumor growth was assessed by (i) depleting mouse macrophages in nude mice with liposomal clodronate injection, and (ii) injecting tumor cells into nude versus NOD- scid -gamma mice...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29188480/a-function-blocking-cd47-antibody-modulates-extracellular-vesicle-mediated-intercellular-signaling-between-breast-carcinoma-cells-and-endothelial-cells
#15
Sukhbir Kaur, Abdel G Elkahloun, Satya P Singh, Anush Arakelyan, David D Roberts
Tumor cells release extracellular vesicles (EVs) into the tumor microenvironment that may facilitate malignant progression and metastasis. Breast carcinoma EVs express high levels of the thrombospondin-1 and signal regulatory protein-α receptor CD47, which is the target of several experimental therapeutics currently in clinical trials. We analyzed changes in gene expression and function in human umbilical vein endothelial cells (HUVEC) induced by treatment with EVs derived from breast carcinoma cells and the effects of the function-blocking CD47 antibody B6H12 on the resulting intercellular communication...
March 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29182441/elimination-of-tumor-by-cd47-pd-l1-dual-targeting-fusion-protein-that-engages-innate-and-adaptive-immune-responses
#16
Boning Liu, Huaizu Guo, Jin Xu, Ting Qin, Qingcheng Guo, Nana Gu, Dapeng Zhang, Weizhu Qian, Jianxin Dai, Sheng Hou, Hao Wang, Yajun Guo
The host immune system generally serves as a barrier against tumor formation. Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known as the "don't eat me" signal, to the innate immune system. These and similar immune checkpoints are often overexpressed on human tumors. Thus, dual targeting both innate and adaptive immune checkpoints would likely maximize anti-tumor therapeutic effect and elicit more durable responses...
February 2018: MAbs
https://www.readbyqxmd.com/read/29158380/anti-sirp%C3%AE-antibody-immunotherapy-enhances-neutrophil-and-macrophage-antitumor-activity
#17
Nan Guo Ring, Dietmar Herndler-Brandstetter, Kipp Weiskopf, Liang Shan, Jens-Peter Volkmer, Benson M George, Melanie Lietzenmayer, Kelly M McKenna, Tejaswitha J Naik, Aaron McCarty, Yunjiang Zheng, Aaron M Ring, Richard A Flavell, Irving L Weissman
Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47 expressed on tumors and normal tissues. We therefore developed the monoclonal antibody KWAR23, which binds human SIRPα with high affinity and disrupts its binding to CD47...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29065481/cd47-car-t-cells-effectively-kill-target-cancer-cells-and-block-pancreatic-tumor-growth
#18
Vita Golubovskaya, Robert Berahovich, Hua Zhou, Shirley Xu, Hizkia Harto, Le Li, Cheng-Chi Chao, Mike Ming Mao, Lijun Wu
CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen...
October 21, 2017: Cancers
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
#19
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
#20
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 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 hour 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...
April 2018: American Journal of Transplantation
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