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https://www.readbyqxmd.com/read/27895507/fc-gamma-receptors-glycobiology-and-therapeutic-prospects
#1
REVIEW
Jerrard M Hayes, Mark R Wormald, Pauline M Rudd, Gavin P Davey
Therapeutic antibodies hold great promise for the treatment of cancer and autoimmune diseases, and developments in antibody-drug conjugates and bispecific antibodies continue to enhance treatment options for patients. Immunoglobulin (Ig) G antibodies are proteins with complex modifications, which have a significant impact on their function. The most important of these modifications is glycosylation, the addition of conserved glycans to the antibody Fc region, which is critical for its interaction with the immune system and induction of effector activities such as antibody-dependent cell cytotoxicity, complement activation and phagocytosis...
2016: Journal of Inflammation Research
https://www.readbyqxmd.com/read/27742794/fcgr-polymorphisms-influence-response-to-il-2-in-metastatic-renal-cell-carcinoma
#2
Amy K Erbe, Wei Wang, Jacob Goldberg, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, James W Mier, David J Panka, David F McDermott, Paul M Sondel
BACKGROUND: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated anti-tumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of cancer patients treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines...
October 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27712994/identification-of-high-affinity-anti-cd16a-allotype-independent-human-antibody-domains
#3
Wei Li, Hongjia Yang, Dimiter S Dimitrov
CD16A (FcγRIIIA) is an activating receptor mostly expressed on natural killer (NK) cells and monocytes/macrophages. It can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) through low-affinity interaction with human immunoglobulin G (IgG) Fc. It can also mediate cell lysis if NK cells are guided by bispecific killer cells engagers (BiKEs). BiKEs showed some success in clinical trials of cancer and are promising candidate therapeutics. However, currently reported BiKEs are based on antibody fragments (scFvs) of relatively large size...
October 3, 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/27564103/cd64-directed-microtubule-associated-protein-tau-kills-leukemic-blasts-ex-vivo
#4
Radoslav Mladenov, Dmitrij Hristodorov, Christian Cremer, Gerrit Gresch, Elena Grieger, Lea Schenke, Diana Klose, Manal Amoury, Mira Woitok, Edgar Jost, Tim H Brümmendorf, Rolf Fendel, Rainer Fischer, Christoph Stein, Theo Thepen, Stefan Barth
Fc gamma receptor I (FcγRI, CD64) is a well-known target antigen for passive immunotherapy against acute myeloid leukemia and chronic myelomonocytic leukemia. We recently reported the preclinical immunotherapeutic potential of microtubule associated protein tau (MAP) against a variety of cancer types including breast carcinoma and Hodgkin's lymphoma. Here we demonstrate that the CD64-directed human cytolytic fusion protein H22(scFv)-MAP kills ex vivo 15-50% of CD64+ leukemic blasts derived from seven myeloid leukemia patients...
August 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27007159/genetic-overlap-between-type-2-diabetes-and-major-depressive-disorder-identified-by-bioinformatics-analysis
#5
Hong-Fang Ji, Qi-Shuai Zhuang, Liang Shen
Our study investigated the shared genetic etiology underlying type 2 diabetes (T2D) and major depressive disorder (MDD) by analyzing large-scale genome wide association studies statistics. A total of 496 shared SNPs associated with both T2D and MDD were identified at p-value ≤ 1.0E-07. Functional enrichment analysis showed that the enriched pathways pertained to immune responses (Fc gamma R-mediated phagocytosis, T cell and B cell receptors signaling), cell signaling (MAPK, Wnt signaling), lipid metabolism, and cancer associated pathways...
April 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27004307/correlation-of-fc%C3%AE-riiia-polymorphisms-to-the-response-of-rituximab-in-thai-patients-with-diffuse-large-b-cell-lymphoma
#6
Naruemol Angsirisak, Supeecha Wittayalertpanya, Wacharee Limpanasithikul, Udomsak Bunworasate, Danai Owattanapanich
BACKGROUND: Rituximab is an anti-CD20 chimeric antibody widely used in combination with CHOP regimen for the treatment of diffuse large B-cell lymphoma (DLBCL). It is suggested that this antibody destroys B lymphoma cells mainly by antibody dependent cellular cytotoxicity (ADCC) mechanism via the binding of the drug to FC gamma IIIa receptor (FcγRIIIa) on natural killer (NK) cells, affected to kill cancer cells. The FcγRIIIa has genetic polymorphism at nucleotide position 559 (G559T or V158F or rs396991) have shown influence on the binding and efficacy of rituximab...
December 2015: Journal of the Medical Association of Thailand, Chotmaihet Thangphaet
https://www.readbyqxmd.com/read/26942051/effective-combination-treatment-of-gd2-expressing-neuroblastoma-and-ewing-s-sarcoma-using-anti-gd2-ch14-18-cho-antibody-with-v%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-t-cells
#7
Jonathan P H Fisher, Barry Flutter, Florian Wesemann, Jennifer Frosch, Claudia Rossig, Kenth Gustafsson, John Anderson
Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/26579227/cetuximab-ameliorates-suppressive-phenotypes-of-myeloid-antigen-presenting-cells-in-head-and-neck-cancer-patients
#8
Jing Li, Raghvendra M Srivastava, Abhinav Ettyreddy, Robert L Ferris
BACKGROUND: Myeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity...
2015: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/26545243/evaluation-of-high-throughput-genomic-assays-for-the-fc-gamma-receptor-locus
#9
Chantal E Hargreaves, Chisako Iriyama, Matthew J J Rose-Zerilli, Sietse Q Nagelkerke, Khiyam Hussain, Rosalind Ganderton, Charlotte Lee, Lee R Machado, Edward J Hollox, Helen Parker, Kate V Latham, Taco W Kuijpers, Kathleen N Potter, Sarah E Coupland, Andrew Davies, Michael Stackpole, Melanie Oates, Andrew R Pettitt, Martin J Glennie, Mark S Cragg, Jonathan C Strefford
Cancer immunotherapy has been revolutionised by the use monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner...
2015: PloS One
https://www.readbyqxmd.com/read/26284063/nk-cell-mediated-antibody-dependent-cellular-cytotoxicity-in-cancer-immunotherapy
#10
REVIEW
Wei Wang, Amy K Erbe, Jacquelyn A Hank, Zachary S Morris, Paul M Sondel
Natural killer (NK) cells play a major role in cancer immunotherapies that involve tumor-antigen targeting by monoclonal antibodies (mAbs). NK cells express a variety of activating and inhibitory receptors that serve to regulate the function and activity of the cells. In the context of targeting cells, NK cells can be "specifically activated" through certain Fc receptors that are expressed on their cell surface. NK cells can express FcγRIIIA and/or FcγRIIC, which can bind to the Fc portion of immunoglobulins, transmitting activating signals within NK cells...
2015: Frontiers in Immunology
https://www.readbyqxmd.com/read/26031575/modulating-the-innate-immune-activity-in-murine-tumor-microenvironment-by-a-combination-of-inducer-molecules-attached-to-microparticles
#11
Ehud Shahar, Raphael Gorodetsky, Elina Aizenshtein, Lior Lalush, Jacob Pitcovski
Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). A promising route to overcome those drawbacks may be by activating innate immune cells (IIC) in the TME, toward tumor destruction. Studies have shown the ability to "re-educate" pro-tumor-activated IIC toward antitumor responses. The current research aims to stimulate such activation using a combination of innate activators loaded onto microparticles (MP). Four inducers of Toll-like receptors 4 and 7, complement C5a receptor (C5aR) and gamma Fc receptor and their combinations were loaded on MP, and their influence on immune cell activation evaluated...
September 2015: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/25978952/aqueous-extract-of-orostachys-japonicus-a-berger-exerts-immunostimulatory-activity-in-raw-264-7-macrophages
#12
Hye-Jin Park, Hye Jeong Yang, Ki Hyun Kim, Sang Hee Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (Crassulaceae) (OJ), well-known as Wa-song in Korea is a medicinal plant with immunoregulatory, anti-febrile, antidote, and anti-cancer activities. This study was aimed at evaluating the immunostimulatory effect of O. japonicus A. Berger and its possible mechanisms of action. MATERIALS AND METHODS: To evaluate the effect of OJ aqueous extract on macrophage activity, we evaluated the modulation of macrophage activation state by observing structural (phagocytic activities) and the production of nitric oxide increase...
July 21, 2015: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/25962696/fc-gamma-receptor-polymorphism-and-gene-expression-of-peripheral-blood-mononuclear-cells-in-patients-with-her2-positive-metastatic-breast-cancer-receiving-single-agent-trastuzumab
#13
Chikako Shimizu, Kaoru Mogushi, Masaki Suimye Morioka, Harukaze Yamamoto, Kenji Tamura, Yasuhiro Fujiwara, Hiroshi Tanaka
AIM: The aim of this study was to investigate gene expression in the peripheral blood mononuclear cells (PBMCs) of patients with HER2-positive breast cancer receiving trastuzumab. We also evaluated the effect of Fc-gamma receptor genotype on trastuzumab-driven gene expression. MATERIALS AND METHODS: Gene expression was assessed by microarray analyses before and after administration of single-agent trastuzumab in 34 patients with metastatic HER2-positive breast cancer who were genotyped for Fc-gamma receptor (FcGR) IIA H131R and FcGRIIIA V158F...
July 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/25792524/novel-strategies-for-inhibiting-pd-1-pathway-mediated-immune-suppression-while-simultaneously-delivering-activating-signals-to-tumor-reactive-t-cells
#14
REVIEW
Suzanne Ostrand-Rosenberg, Lucas A Horn, Juan A Alvarez
We previously developed cell-based vaccines as therapeutics for metastatic cancers. The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain. The vaccines showed some efficacy in mice with sarcoma, melanoma, and breast cancer and activated MHC class II syngeneic T cells from breast, lung, and melanoma patients. During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells...
October 2015: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/25514603/chemically-synthesized-molecules-with-the-targeting-and-effector-functions-of-antibodies
#15
Patrick J McEnaney, Kelly J Fitzgerald, Andrew X Zhang, Eugene F Douglass, Weifang Shan, Aaron Balog, Mariya D Kolesnikova, David A Spiegel
This article reports the design, synthesis, and evaluation of a novel class of molecules of intermediate size (approximately 7000 Da), which possess both the targeting and effector functions of antibodies. These compounds—called synthetic antibody mimics targeting prostate cancer (SyAM-Ps)—bind simultaneously to prostate-specific membrane antigen and Fc gamma receptor I, thus eliciting highly selective cancer cell phagocytosis. SyAMs have the potential to combine the advantages of both small-molecule and biologic therapies, and may address many drawbacks associated with available treatments for cancer and other diseases...
December 31, 2014: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/25484045/multivalent-nanobodies-targeting-death-receptor-5-elicit-superior-tumor-cell-killing-through-efficient-caspase-induction
#16
Heather A Huet, Joseph D Growney, Jennifer A Johnson, Jing Li, Sanela Bilic, Lance Ostrom, Mohammad Zafari, Colleen Kowal, Guizhi Yang, Axelle Royo, Michael Jensen, Bruno Dombrecht, Kris R A Meerschaert, Joost A Kolkman, Karen D Cromie, Rebecca Mosher, Hui Gao, Alwin Schuller, Randi Isaacs, William R Sellers, Seth A Ettenberg
Multiple therapeutic agonists of death receptor 5 (DR5) have been developed and are under clinical evaluation. Although these agonists demonstrate significant anti-tumor activity in preclinical models, the clinical efficacy in human cancer patients has been notably disappointing. One possible explanation might be that the current classes of therapeutic molecules are not sufficiently potent to elicit significant response in patients, particularly for dimeric antibody agonists that require secondary cross-linking via Fcγ receptors expressed on immune cells to achieve optimal clustering of DR5...
2014: MAbs
https://www.readbyqxmd.com/read/25278812/cd28-cd45ra-null-dim-and-natural-killer-like-cd8-t-cells-are-increased-in-peripheral-blood-of-women-with-low-grade-cervical-lesions
#17
Maria Luisa Pita-Lopez, Pablo Cesar Ortiz-Lazareno, Monica Navarro-Meza, Felipe Santoyo-Telles, Oscar Peralta-Zaragoza
BACKGROUND: In response to antigen naive CD8+, T cells differentiate into effector cells, which express Natural killer (NK) receptors, lose CD28 expression, and die by apoptosis. However, in smaller quantities, the cells are retained for subsequent exposure to the same antigen. Knowledge is limited regarding whether the percentages of CD28-, Effector memory (EMRA(null/dim)), and the CD16+/CD56 + CD8+ T cells of women with low-grade cervical lesions are altered at a systemic level...
2014: Cancer Cell International
https://www.readbyqxmd.com/read/25220345/a-new-bispecific-antibody-targeting-non-overlapping-epitopes-on-igf2-design-in-vitro-characterization-and-pharmacokinetics-in-macaques
#18
Yang Feng, Qi Zhao, Weizao Chen, Yanping Wang, Karalyne Crowder, Dimiter S Dimitrov
The insulin-like growth factor 2 (IGF2) is an important target for cancer therapy. We have previously proposed an approach for fast and irreversible removal of IGF2 from the circulation by using monoclonal antibodies (mAbs) that bind to two or more non-overlapping epitopes on the same molecule. We provided initial evidence for the formation of oligomeric antibody-ligand complexes that can bind to cells expressing Fc gamma receptors (FcγRs) with high avidity using an antibody domain with relatively low affinity as one of the anti-IGF2 mAbs...
December 2014: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/25217158/fc-optimized-nkg2d-fc-constructs-induce-nk-cell-antibody-dependent-cellular-cytotoxicity-against-breast-cancer-cells-independently-of-her2-neu-expression-status
#19
Stefanie Raab, Julia Steinbacher, Benjamin J Schmiedel, Philaretos C Kousis, Alexander Steinle, Gundram Jung, Ludger Grosse-Hovest, Helmut R Salih
The ability of NK cells to mediate Ab-dependent cellular cytotoxicity (ADCC) largely contributes to the clinical success of antitumor Abs, including trastuzumab, which is approved for the treatment of breast cancer with HER2/neu overexpression. Notably, only ∼25% of breast cancer patients overexpress HER2/neu. Moreover, HER2/neu is expressed on healthy cells, and trastuzumab application is associated with side effects. In contrast, the ligands of the activating immunoreceptor NKG2D (NKG2DL) are selectively expressed on malignant cells...
October 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25191216/new-roles-for-fc-receptors-in-neurodegeneration-the-impact-on-immunotherapy-for-alzheimer-s-disease
#20
REVIEW
James P Fuller, Jeffrey B Stavenhagen, Jessica L Teeling
There are an estimated 18 million Alzheimer's disease (AD) sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterized by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterized by deposits of amyloid beta (Aβ), neurofibrillary tangles, and neuroinflammation. Active immunization or passive immunization against Aβ leads to the clearance of deposits in transgenic mice expressing human Aβ...
2014: Frontiers in Neuroscience
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