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CD47 antibody

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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
#1
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
#2
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...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28275508/targeting-cd47-the-achievements-and-concerns-of-current-studies-on-cancer-immunotherapy
#3
COMMENT
Yuting Huang, Yuchi Ma, Peng Gao, Zhi Yao
Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction...
February 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#4
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28208074/cd47-limits-antibody-dependent-phagocytosis-against-non-malignant-b-cells
#5
Sandra Gallagher, Sean Turman, Kristen Lekstrom, Susan Wilson, Ronald Herbst, Yue Wang
Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28186432/development-of-anti-cd47-single-chain-variable-fragment-targeted-magnetic-nanoparticles-for-treatment-of-human-bladder-cancer
#6
Gashin Rezaei, Mahdi Habibi-Anbouhi, Morteza Mahmoudi, Kayhan Azadmanesh, Shima Moradi-Kalbolandi, Mahdi Behdani, Leila Ghazizadeh, Mohsen Abolhassani, Mohammad Ali Shokrgozar
AIM: To develop a novel anti-CD47 single-chain variable fragment (scFv) functionalized magnetic nanoparticles (MNPs) for targeting bladder cell lines and its applicability in thermotherapy. MATERIAL & METHODS: An immunized murine antibody phage display library was constructed and screened to isolate anti-CD47 binders. A scFv was selected and conjugated to MNPs which was then utilized to discriminate CD47(+) bladder cells along with assessing its efficacy in thermotherapy...
February 10, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28161480/multifunctionalized-iron-oxide-nanoparticles-for-selective-targeting-of-pancreatic-cancer-cells
#7
Sara Trabulo, Antonio Aires, Alexandra Aicher, Christopher Heeschen, Aitziber L Cortajarena
Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28153099/selective-blockade-of-the-ubiquitous-checkpoint-receptor-cd47-is-enabled-by-dual-targeting-bispecific-antibodies
#8
Elie Dheilly, Valéry Moine, Lucile Broyer, Susana Salgado-Pires, Zoë Johnson, Anne Papaioannou, Laura Cons, Sébastien Calloud, Stefano Majocchi, Robert Nelson, François Rousseau, Walter Ferlin, Marie Kosco-Vilbois, Nicolas Fischer, Krzysztof Masternak
CD47 is a ubiquitously expressed immune checkpoint receptor that is often upregulated in cancer. CD47 interacts with its counter-receptor SIRPα on macrophages and other myeloid cells to inhibit cancer cell phagocytosis and drive immune evasion. To overcome tolerability and "antigen sink" issues arising from widespread CD47 expression, we generated dual-targeting bispecific antibodies that selectively block the CD47-SIRPα interaction on malignant cells expressing a specific tumor-associated antigen; e.g., CD19 or mesothelin...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#9
Hayato Iwase, Hong Liu, Eva Schmelzer, Mohamed Ezzelarab, Martin Wijkstrom, Hidetaka Hara, Whayoung Lee, Jagjit Singh, Cassandra Long, Eric Lagasse, Jörg C Gerlach, David K C Cooper, Bruno Gridelli
BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28100392/replication-study-the-cd47-signal-regulatory-protein-alpha-sirpa-interaction-is-a-therapeutic-target-for-human-solid-tumors
#10
Stephen K Horrigan
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors "(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28097229/anti-sirp%C3%AE-antibodies-as-a-potential-new-tool-for-cancer-immunotherapy
#11
Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei-Ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per-Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki
Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28077173/is-cd47-an-innate-immune-checkpoint-for-tumor-evasion
#12
REVIEW
Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang-Xin Fu
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28076333/surgical-debulking-promotes-recruitment-of-macrophages-and-triggers-glioblastoma-phagocytosis-in-combination-with-cd47-blocking-immunotherapy
#13
Huaiyang Zhu, Lina Leiss, Ning Yang, Cecilie B Rygh, Siddhartha S Mitra, Samuel H Cheshier, Irving L Weissman, Bin Huang, Hrvoje Miletic, Rolf Bjerkvig, Per Ø Enger, Xingang Li, Jian Wang
Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking in preclinical models. Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. Orthotopic patient-derived xenograft tumors expressing CD47 were resected at 4 weeks after implantation and immediately thereafter treated with anti-CD47 or control antibodies injected into the cavity...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061465/sirp%C3%AE-antibody-fusion-proteins-stimulate-phagocytosis-and-promote-elimination-of-acute-myeloid-leukemia-cells
#14
Laia Pascual Ponce, Nadja C Fenn, Nadine Moritz, Christina Krupka, Jan-Hendrik Kozik, Kirsten Lauber, Marion Subklewe, Karl-Peter Hopfner
CD47, expressed on a variety of tumor cells, confers immune resistance by delivering an inhibitory "don't eat me" signal to phagocytic cells via its myeloid-specific receptor SIRPα. Recent studies have shown that blocking the CD47-SIRPα axis with CD47-directed antibodies or antibody-derivatives enhances phagocytosis and increases antitumor immune effects. However, CD47 expression on healthy cells creates an antigen sink and potential sites of toxicity, limiting the efficacy of CD47-directed therapies. In this study, we first characterized CD47 expression in Acute Myeloid Leukemia (AML) patients (n = 213) and found that CD47 is highly expressed on both AML bulk and stem cells irrespective of the disease state...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/27929051/reduced-expression-of-monocyte-cd200r-is-associated-with-enhanced-proinflammatory-cytokine-production-in-sarcoidosis
#15
Simon D Fraser, Laura R Sadofsky, Paul M Kaye, Simon P Hart
In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27863402/a-fully-human-anti-cd47-blocking-antibody-with-therapeutic-potential-for-cancer
#16
Dadi Zeng, Qiang Sun, Ang Chen, Jiangfeng Fan, Xiaopeng Yang, Lei Xu, Peng Du, Weiyi Qiu, Weicai Zhang, Shuang Wang, Zhiwei Sun
CD47/SIRPα interaction serves as an immune checkpoint for macrophage-mediated phagocytosis. Mouse anti-CD47 blocking antibodies had demonstrated potent efficacy in the treatment of both leukemic and solid tumors in preclinical experimentations, and therefore had moved forward rapidly into clinical trials. However, a fully human blocking antibody, which meets clinical purpose better, has not been reported for CD47 up to date. In this study, we reported the isolation of a fully human anti-CD47 blocking antibody, ZF1, from a phage display library...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856600/tti-621-sirp%C3%AE-fc-a-cd47-blocking-innate-immune-checkpoint-inhibitor-with-broad-antitumor-activity-and-minimal-erythrocyte-binding
#17
Penka S Petrova, Natasja Nielsen Viller, Mark Wong, Xinli Pang, Gloria H Y Lin, Karen Dodge, Vien Chai, Hui Chen, Vivian Lee, Violetta House, Noel T Vigo, Debbie Jin, Tapfuma Mutukura, Marilyse Charbonneau, Tran Truong, Stephane Viau, Lisa D Johnson, Emma Linderoth, Eric L Sievers, Saman Maleki Vareki, Rene Figueredo, Macarena Pampillo, James Koropatnick, Suzanne Trudel, Nathan Mbong, Liqing Jin, Jean C Y Wang, Robert A Uger
PURPOSE: The ubiquitously expressed transmembrane glycoprotein CD47 delivers an anti-phagocytic (do not eat) signal by binding signal-regulatory protein α (SIRPα) on macrophages. CD47 is overexpressed in cancer cells and its expression is associated with poor clinical outcomes. TTI-621 (SIRPαFc) is a fully human recombinant fusion protein that blocks the CD47-SIRPα axis by binding to human CD47 and enhancing phagocytosis of malignant cells. Blockade of this inhibitory axis using TTI-621 has emerged as a promising therapeutic strategy to promote tumor cell eradication...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27856424/eradication-of-canine-diffuse-large-b-cell-lymphoma-in-a-murine-xenograft-model-with-cd47-blockade-and-anti-cd20
#18
Kipp Weiskopf, Katie L Anderson, Daisuke Ito, Peter J Schnorr, Hirotaka Tomiyasu, Aaron M Ring, Kristin Bloink, Jem Efe, Sarah Rue, David Lowery, Amira Barkal, Susan Prohaska, Kelly M McKenna, Ingrid Cornax, Timothy D O'Brien, M Gerard O'Sullivan, Irving L Weissman, Jaime F Modiano
Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined the combination of CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma. The CD47/SIRPα axis is an immune checkpoint that regulates macrophage activation. In humans, CD47 is expressed on cancer cells and enables evasion from phagocytosis...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27855370/cd47-is-a-potential-target-for-the-treatment-of-laryngeal-squamous-cell-carcinoma
#19
ChunPing Yang, ShuFeng Gao, HaiZhen Zhang, Lian Xu, JianGuo Liu, Meiqun Wang, ShaoRong Zhang
BACKGROUND/AIMS: This study aims to investigate the effect of CD47 on the development of laryngeal squamous cell carcinoma (LSCC) and the therapeutic potential of monoclonal antibody against CD47 and its ligand SIRPα in the treatment of LSCC. METHODS: We firstly detected the expressions of CD47 mRNA and protein in LSCC and para-carcinoma tissues, introduced the most efficient CD47siRNA sequence into LSCC cells by lentiviral transfection and employed three monoclonal antibodies to evaluate their anti-LSCC effects in vitro and in vivo...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27784127/cd44-as-a-potential-screening-marker-for-preliminary-differentiation-between-congenital-dyserythropoietic-anemia-type-ii-and-hereditary-spherocytosis
#20
B K Singleton, M Ahmed, C A Green, H Heimpel, M J Woźniak, L Ranjha, F Seeney, A Bomford, P Mehta, A Guest, R Mushens, M-J King
BACKGROUND: Bone marrow examination has been the confirmatory test for congenital dyserythropoietic anemia type II (CDAII). Occasional spherocytes on peripheral blood smear can confound the diagnosis. Since a screening test is still unavailable, we explored the feasibility of using flow cytometry as a preliminary screening method. METHODS: Thirteen monoclonal antibodies with specificities for eight erythrocyte membrane proteins were used in FACS analysis to probe the cellular features of red cells from CDAII, normal adults, hereditary spherocytosis (HS), and cord red cells...
October 26, 2016: Cytometry. Part B, Clinical Cytometry
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