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fc gamma receptor cancer

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https://www.readbyqxmd.com/read/28496440/fc%C3%AE-chimeric-receptor-engineered-t-cells-methodology-advantages-limitations-and-clinical-relevance
#1
REVIEW
Sara Caratelli, Tommaso Sconocchia, Roberto Arriga, Andrea Coppola, Giulia Lanzilli, Davide Lauro, Adriano Venditti, Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Soldano Ferrone, Giuseppe Sconocchia
For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient's immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient's immune system can recognize and reject his tumor if appropriate strategies are implemented...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28410988/fc-optimized-anti-cd25-depletes-tumor-infiltrating-regulatory-t-cells-and-synergizes-with-pd-1-blockade-to-eradicate-established-tumors
#2
Frederick Arce Vargas, Andrew J S Furness, Isabelle Solomon, Kroopa Joshi, Leila Mekkaoui, Marta H Lesko, Enrique Miranda Rota, Rony Dahan, Andrew Georgiou, Anna Sledzinska, Assma Ben Aissa, Dafne Franz, Mariana Werner Sunderland, Yien Ning Sophia Wong, Jake Y Henry, Tim O'Brien, David Nicol, Ben Challacombe, Stephen A Beers, Samra Turajlic, Martin Gore, James Larkin, Charles Swanton, Kerry A Chester, Martin Pule, Jeffrey V Ravetch, Teresa Marafioti, Karl S Peggs, Sergio A Quezada
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28405505/medi1873-a-potent-stabilized-hexameric-agonist-of-human-gitr-with-regulatory-t-cell-targeting-potential
#3
Natalie J Tigue, Lisa Bamber, John Andrews, Samantha Ireland, James Hair, Edward Carter, Sudharsan Sridharan, Jelena Jovanović, D Gareth Rees, Jeremy S Springall, Emilie Solier, Yi-Ming Li, Matthieu Chodorge, David Perez-Martinez, Daniel R Higazi, Michael Oberst, Maureen Kennedy, Chelsea M Black, Li Yan, Martin Schwickart, Shaun Maguire, Jennifer A Cann, Lolke de Haan, Lesley L Young, Tristan Vaughan, Robert W Wilkinson, Ross Stewart
Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is part of a system of signals involved in controlling T-cell activation. Targeting and agonizing GITR in mice promotes antitumor immunity by enhancing the function of effector T cells and inhibiting regulatory T cells. Here, we describe MEDI1873, a novel hexameric human GITR agonist comprising an IgG1 Fc domain, a coronin 1A trimerization domain and the human GITRL extracellular domain (ECD). MEDI1873 was optimized through systematic testing of different trimerization domains, aglycosylation of the GITRL ECD and comparison of different Fc isotypes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28341790/tumor-associated-macrophages-can-contribute-to-antitumor-activity-through-fc%C3%AE-r-mediated-processing-of-antibody-drug-conjugates
#4
Fu Li, Michelle Ulrich, Mechthild Jonas, Ivan J Stone, Germein Linares, Xinqun Zhang, Lori Westendorf, Dennis R Benjamin, Che-Leung Law
The primary mechanism of antibody-drug conjugates (ADCs) is targeted delivery of a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the tumor microenvironment likely plays a role in ADC penetration, distribution, and processing and thus impacts the overall antitumor activity. Here, we report on the potential contribution of Fc-FcγR interactions between ADCs and tumor-associated macrophages (TAMs) to the preclinical antitumor activities of ADCs. In the CD30+ L-428 Hodgkin lymphoma model, anti-CD30-vcMMAE and a non-binding control (hIgG-vcMMAE) demonstrated similar antitumor activity as well as similar payload release in the tumors...
March 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28184223/fc-engineering-for-developing-therapeutic-bispecific-antibodies-and-novel-scaffolds
#5
REVIEW
Hongyan Liu, Abhishek Saxena, Sachdev S Sidhu, Donghui Wu
Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018347/advances-in-therapeutic-fc-engineering-modulation-of-igg-associated-effector-functions-and-serum-half-life
#6
REVIEW
Abhishek Saxena, Donghui Wu
Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27895507/fc-gamma-receptors-glycobiology-and-therapeutic-prospects
#7
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-il2-in-metastatic-renal-cell-carcinoma
#8
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
Purpose: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of patients with cancer 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...
May 1, 2017: 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
#9
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
#10
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...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27007159/genetic-overlap-between-type-2-diabetes-and-major-depressive-disorder-identified-by-bioinformatics-analysis
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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