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CD47 antibody

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https://www.readbyqxmd.com/read/27863402/a-fully-human-anti-cd47-blocking-antibody-with-therapeutic-potential-for-cancer
#1
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...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856600/tti-621-sirp%C3%AE-fc-a-cd47-blocking-innate-immune-checkpoint-inhibitor-with-broad-anti-tumor-activity-and-minimal-erythrocyte-binding
#2
Penka S Petrova, Natasja N 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, Stéphane 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 over-expressed 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
#3
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...
November 14, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27855370/cd47-is-a-potential-target-for-the-treatment-of-laryngeal-squamous-cell-carcinoma
#4
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
#5
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
https://www.readbyqxmd.com/read/27742621/tsp1-cd47-signaling-is-upregulated-in-clinical-pulmonary-hypertension-and-contributes-to-pulmonary-arterial-vasculopathy-and-dysfunction
#6
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27728760/surface-glycoproteins-of-exosomes-shed-by-myeloid-derived-suppressor-cells-contribute-to-function
#7
Sitara Chauhan, Steven Danielson, Virginia Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Catherine Fenselau
In this report we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSC), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSC. We report successful modification of a surface chemistry method for use with exosomes, and identify twenty-one surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSC. These glycoprotein identities and functionalities are compared with ninty-three N-linked glycoproteins identified on the surface of the parental cells...
October 11, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27510901/hematopoietic-stem-cell-transplantation-in-immunocompetent-hosts-without-radiation-or-chemotherapy
#8
Akanksha Chhabra, Aaron M Ring, Kipp Weiskopf, Peter John Schnorr, Sydney Gordon, Alan C Le, Hye-Sook Kwon, Nan Guo Ring, Jens Volkmer, Po Yi Ho, Serena Tseng, Irving L Weissman, Judith A Shizuru
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti-c-Kit conditioning to fully immunocompetent mice...
August 10, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27477289/antibody-therapy-targeting-cd47-and-cd271-effectively-suppresses-melanoma-metastasis-in-patient-derived-xenografts
#9
Michael Ngo, Arum Han, Anita Lakatos, Debashis Sahoo, Stephanie J Hachey, Kipp Weiskopf, Andrew H Beck, Irving L Weissman, Alexander D Boiko
The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271(+) melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts...
August 9, 2016: Cell Reports
https://www.readbyqxmd.com/read/27437576/cd47-blocking-antibodies-restore-phagocytosis-and-prevent-atherosclerosis
#10
Yoko Kojima, Jens-Peter Volkmer, Kelly McKenna, Mete Civelek, Aldons Jake Lusis, Clint L Miller, Daniel Direnzo, Vivek Nanda, Jianqin Ye, Andrew J Connolly, Eric E Schadt, Thomas Quertermous, Paola Betancur, Lars Maegdefessel, Ljubica Perisic Matic, Ulf Hedin, Irving L Weissman, Nicholas J Leeper
Atherosclerosis is the disease process that underlies heart attack and stroke. Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Why these cells are not cleared remains unknown. Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or 'efferocytosis'. We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models...
August 4, 2016: Nature
https://www.readbyqxmd.com/read/27331362/attenuation-of-ischemia-reperfusion-injury-and-improvement-of-survival-in-recipients-of-steatotic-rat-livers-using-cd47-monoclonal-antibody
#11
Zhenyu Xiao, Babak Banan, Min Xu, Jianluo Jia, Pamela T Manning, Ronald R Hiebsch, Muthukumar Gunasekaran, Gundumi A Upadhya, William A Frazier, Thalachallour Mohanakumar, Yiing Lin, William C Chapman
BACKGROUND: Despite the efficacy of orthotopic liver transplantation in the treatment of end-stage liver diseases, its therapeutic utility is severely limited by the availability of donor organs. The ability to rehabilitate marginal organs, such as steatotic allografts, has the potential to address some of the supply limitations of available organs for transplantation. Steatotic livers are more susceptible to ischemia-reperfusion injury (IRI), which is exacerbated by the thrombospondin-1/CD47 pathway through inhibition of nitric oxide signaling...
July 2016: Transplantation
https://www.readbyqxmd.com/read/27322955/relationship-between-tumor-associated-macrophage-subsets-and-cd47-expression-in-squamous-cell-carcinoma-of-the-head-and-neck-in-the-tumor-microenvironment
#12
Koichi Sakakura, Hideyuki Takahashi, Kyoichi Kaira, Minoru Toyoda, Takaaki Murata, Hiroshi Ohnishi, Tetsunari Oyama, Kazuaki Chikamatsu
Tumor-associated macrophages (TAM) have been classified into an immunostimulatory M1 subset against microbes and malignancies, and an immunoregulatory M2 subset that secretes immunosuppressive cytokines in order to repair tissues damaged by malignancies. The infiltration of M2 in the tumor microenvironment is known to facilitate immunosuppression and tumor-promoting properties. In the present study, we investigated the phagocytic potential of these macrophage subsets in oral squamous cell carcinoma (OSCC) in relation to the expression of CD47, the 'don't eat me' signal against macrophages...
September 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27302826/re-endoscopic-molecular-imaging-of-human-bladder-cancer-using-a-cd47-antibody
#13
Sam S Chang
No abstract text is available yet for this article.
April 2016: Journal of Urology
https://www.readbyqxmd.com/read/27294525/cd47-blocking-immunotherapies-stimulate-macrophage-mediated-destruction-of-small-cell-lung-cancer
#14
Kipp Weiskopf, Nadine S Jahchan, Peter J Schnorr, Sandra Cristea, Aaron M Ring, Roy L Maute, Anne K Volkmer, Jens-Peter Volkmer, Jie Liu, Jing Shan Lim, Dian Yang, Garrett Seitz, Thuyen Nguyen, Di Wu, Kevin Jude, Heather Guerston, Amira Barkal, Francesca Trapani, Julie George, John T Poirier, Eric E Gardner, Linde A Miles, Elisa de Stanchina, Shane M Lofgren, Hannes Vogel, Monte M Winslow, Caroline Dive, Roman K Thomas, Charles M Rudin, Matt van de Rijn, Ravindra Majeti, K Christopher Garcia, Irving L Weissman, Julien Sage
Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPα using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture...
July 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27283989/cd47-deficiency-in-tumor-stroma-promotes-tumor-progression-by-enhancing-angiogenesis
#15
Lu Gao, Kexin Chen, Qi Gao, Xiaodan Wang, Jian Sun, Yong-Guang Yang
CD47 is a transmembrane protein that functions as a receptor for thrombospondin-1 (TSP1) and a ligand for inhibitory receptor signal-regulatory protein-α (SIRPα). Blocking the interaction between CD47 on tumor cells and SIRPα on macrophages has been shown to induce antitumor responses. Here we investigated the role of CD47 expression in tumor stroma in tumorigenesis by comparing tumor growth in wild-type (WT) and CD47-deficient mice after subcutaneous injection of syngeneic prostate cancer cells. We found that CD47 deficiency in tumor stromal endothelial cells enhances angiogenesis, leading to suppressed tumor necrosis formation and accelerated tumor progression...
June 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27259369/cd47-regulates-renal-tubular-epithelial-cell-self-renewal-and-proliferation-following-renal-ischemia-reperfusion
#16
Natasha M Rogers, Zheng J Zhang, Jiao-Jing Wang, Angus W Thomson, Jeffrey S Isenberg
Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury...
August 2016: Kidney International
https://www.readbyqxmd.com/read/27199114/physiological-levels-of-thrombospondin-1-decrease-no-dependent-vasodilation-in-coronary-microvessels-from-aged-rats
#17
Chris Nevitt, Grant McKenzie, Katelyn Christian, Jeff Austin, Sarah Hencke, James Hoying, Amanda LeBlanc
Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of CD47, has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking CD47 will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27194758/cd47-plays-a-role-as-a-negative-regulator-in-inducing-protective-immune-responses-to-vaccination-against-influenza-virus
#18
Young-Tae Lee, Eun-Ju Ko, Youri Lee, Yu-Na Lee, Zhen Bian, Yuan Liu, Sang-Moo Kang
UNLABELLED: An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein α, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice...
August 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27168238/how-one-thing-led-to-another
#19
Irving Weissman
I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs...
May 20, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27163531/divergent-modulation-of-normal-and-neoplastic-stem-cells-by-thrombospondin-1-and-cd47-signaling
#20
REVIEW
Sukhbir Kaur, David D Roberts
Thrombospondin-1 is a secreted matricellular protein that regulates the differentiation and function of many cell types. Thrombospondin-1 is not required for embryonic development, but studies using lineage-committed adult stem cells have identified positive and negative effects of thrombospondin-1 on stem cell differentiation and self-renewal and identified several thrombospondin-1 receptors that mediate these responses. Genetic studies in mice reveal a broad inhibitory role of thrombospondin-1 mediated by its receptor CD47...
May 6, 2016: International Journal of Biochemistry & Cell Biology
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