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Anti CD47 Therapy

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https://www.readbyqxmd.com/read/29754163/inhibition-of-autophagy-potentiated-the-anti-tumor-effects-of-vegf-and-cd47-bispecific-therapy-in-glioblastoma
#1
Xuyao Zhang, Shaofei Wang, Yanyang Nan, Jiajun Fan, Wei Chen, Jingyun Luan, Yichen Wang, Yanxu Liang, Song Li, Wenzhi Tian, Dianwen Ju
Glioblastoma, characterized by extensive microvascular proliferation and invasive tumor growth, is one of the most common and lethal malignancies in adults. Benefits of the conventional anti-angiogenic therapy were only observed in a subset of patients and limited by diverse relapse mechanism. Fortunately, recent advances in cancer immunotherapy have offered new hope for patients with glioblastoma. Herein, we reported a novel dual-targeting therapy for glioblastoma through simultaneous blockade of VEGF and CD47 signaling...
May 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29748606/cd47-ligation-induced-cell-death-in-t-acute-lymphoblastic-leukemia
#2
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
#3
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/29600425/a-novel-bispecific-antibody-fusion-protein-co-targeting-egfr-and-cd47-with-enhanced-therapeutic-index
#4
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...
March 29, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29538621/disrupting-cd47-sirp%C3%AE-axis-alone-or-combined-with-autophagy-depletion-for-the-therapy-of-glioblastoma
#5
Xuyao Zhang, Wei Chen, Jiajun Fan, Shaofei Wang, Zongshu Xian, Jingyun Luan, Yubin Li, Yichen Wang, Yanyang Nan, Man Luo, Song Li, Wenzhi Tian, Dianwen Ju
CD47-targeting immune checkpoint inhibitors have been investigated for immunotherapy of several cancers, glioblastoma, one of the most common tumors in brain, was still a challenge for CD47-targeting therapy. Herein, we reported novel strategies for glioblastoma therapy via blocking CD47-signal regulatory protein-α (SIRPα) by SIRPα-Fc alone or in combination with autophagy inhibition. Our results showed that SIRPα-Fc increased macrophages-triggered cytotoxicity and phagocytosis of glioblastoma cells then elicited potent anti-tumor efficacy...
May 3, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29414673/evolving-targets-for-the-treatment-of-atherosclerosis
#6
REVIEW
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29203951/hypo-fractionated-radiation-magnetic-nanoparticle-hyperthermia-and-a-viral-immunotherapy-treatment-of-spontaneous-canine-cancer
#7
P Jack Hoopes, Karen L Moodie, Alicia A Petryk, James D Petryk, Shawntel Sechrist, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Ashish Rajan, Danielle Dugat, Margaret Crary-Burney, Steven N Fiering
It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component...
January 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/29182441/elimination-of-tumor-by-cd47-pd-l1-dual-targeting-fusion-protein-that-engages-innate-and-adaptive-immune-responses
#8
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
#9
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/29090279/selenium-nanoparticles-induce-suppressed-function-of-tumor-associated-macrophages-and-inhibit-dalton-s-lymphoma-proliferation
#10
Pramod Kumar Gautam, Sanjay Kumar, M S Tomar, Rishi Kant Singh, A Acharya, Sanjay Kumar, B Ram
Selenium Nanoparticle (SeNPs) is reported that it enhances and maintains optimal immune during infection and malignancies. To this end, we examined the role of selenium on TAMS whose anti-tumor function suppressed which favor tumor progression. BALB/c (H2d) strain of mice non-Hodgkin type of Dalton's cell line was used to check the role of carboxlic group induced, synthesized SeNPs on TAMs. Screening of IC50 value was done primarily trypen blue exclusion assay and 50% proliferation of DL cells inhibited 40 ng/ml to 50 ng/...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#11
REVIEW
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
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
#12
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/28952147/genetic-variation-of-human-neutrophil-fc%C3%AE-receptors-and-sirp%C3%AE-in-antibody-dependent-cellular-cytotoxicity-towards-cancer-cells
#13
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...
February 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/28874561/localized-cd47-blockade-enhances-immunotherapy-for-murine-melanoma
#14
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/28815041/-upregulation-of-cd47-by-the-endoplasmic-reticulum-stress-pathway-controls-anti-tumor-immune-responses
#15
Katherine L Cook, David R Soto-Pantoja
We recently demonstrated that targeting the unfolded protein response (UPR) protein GRP78 down-regulates CD47 expression, resulting in increased tumor macrophage infiltration and inhibited resistance to anti-estrogen therapy. We now show new data indicating that anti-estrogen therapy regulates CD47 expression and implicates its ligand, thrombospondin-1, in regulation of tumor macrophage infiltration. Moreover, GRP78 and CD47 co-expression is associated with poor prognosis in breast cancer patients, suggesting the existence of crosstalk between UPR and immunity that regulates therapeutic responses in breast cancer...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28801364/cd47-is-not-over-expressed-in-fibrolamellar-hepatocellular-carcinoma
#16
Tabitha Cooney, Michael C Wei, Arun Rangaswami, Lei Xu, Julien Sage, Florette K Hazard
OBJECTIVES: CD47 is a transmembrane receptor that inhibits phagocytosis. Over-expression of CD47 is associated with an increased risk of tumor growth and metastasis. Clinical trials based on anti-CD47 therapy in adults are underway in a variety of malignancies. CD47 has been shown to be over-expressed in conventional hepatocellular carcinoma (HCC), a common liver tumor in adults. To our knowledge, there have been no studies to evaluate CD47 expression in the fibrolamellar subtype of HCC (FL-HCC), common in children and young adults...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#17
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
December 2017: Cancer Immunology, Immunotherapy: CII
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
#18
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/28550976/cultivation-and-characterization-of-pterygium-as-an-ex-vivo-study-model-for-disease-and-therapy
#19
Natasha Josifovska, Dóra Júlia Szabó, Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Ketil Eriksen, Morten C Moe, Goran Petrovski
PURPOSE: Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. METHODS: Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic- and mesenchymal stem cell markers was performed...
October 2017: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/28484448/anti-cd47-antibody-as-a-targeted-therapeutic-agent-for-human-lung-cancer-and-cancer-stem-cells
#20
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
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