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https://www.readbyqxmd.com/read/29905534/integrated-dna-methylation-and-gene-expression-analysis-identifies-slamf7-as-a-key-regulator-of-atherosclerosis
#1
Zhangyong Xia, Mingliang Gu, Xiaodong Jia, Xiaoting Wang, Chunxia Wu, Jiangwen Guo, Liyong Zhang, Yifeng Du, Jiyue Wang
Atherosclerosis (AS) is a multifactorial disease. Exploration of DNA methylation in regulating gene transcription in a cell type- and stage-specific manner will shed light on understanding the biological processes associated with plaque stability. We identified 174 up-regulated genes with hypo-methylation in the promoter, and 86 down-regulated genes with hyper-methylation in the promoter, in AS vs. healthy controls. Among them, high expression of signaling lymphocytic activation molecule 7 (SLAM7) was examined in carotid plaque vs...
June 13, 2018: Aging
https://www.readbyqxmd.com/read/29859287/molecular-network-pathway-and-functional-analysis-of-time-dependent-gene-changes-related-to-cathepsin-g-exposure-in-neonatal-rat-cardiomyocytes
#2
Sanket Kumar Shukla, Kunal Sikder, Amrita Sarkar, Sankar Addya, Khadija Rafiq
The molecular pathways activated in response to acute cathepsin G (CG) exposure, as well as the mechanisms involved in activation of signaling pathways that culminate in myocyte detachment and apoptosis remain unclear. This study aimed to determine the changes in gene expression patterns associated with time dependent CG exposure to neonatal rat cardiomyocytes (NRCMs). Microarray analysis revealed a total of 451, 572 and 1127 differentially expressed genes after CG exposure at 1, 4 and 8 h respectively. A total of 54 overlapped genes at each time point were mapped by Ingenuity Pathway Analysis (IPA)...
May 30, 2018: Gene
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#3
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29582696/anti-cd38-and-anti-slamf7-the-future-of-myeloma-immunotherapy
#4
Elena Zamagni, Paola Tacchetti, Lucia Pantani, Michele Cavo
the high expression of a number of surface antigens on malignant plasma cells, the bone marrow micro-environment and immune effector T cells, makes these appealing targets for immune therapy with monoclonal antibodies (mAbs). Areas covered: Two mAbs, anti-CD38 daratumumab (Dara) and anti-SLAMF7 elotuzumab (Elo), have achieved recent regulatory approval for relapsed or refractory MM (RRMM) and are currently being explored as possible treatment options in novel combinations and different settings. This review discusses the current landscape and possible development of anti-CD38 and anti-SLAMF7 mAbs...
May 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29531651/elotuzumab-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-with-special-reference-to-its-modes-of-action-and-slamf7-signaling
#5
REVIEW
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29499100/a-cd8%C3%AE-subset-of-cd4-slamf7-cytotoxic-t-cells-is-expanded-in-patients-with-igg4-related-disease-and-decreases-following-glucocorticoid-treatment
#6
Emanuel Della-Torre, Emanuele Bozzalla-Cassione, Clara Sciorati, Eliana Ruggiero, Marco Lanzillotta, Silvia Bonfiglio, Hamid Mattoo, Cory A Perugino, Enrica Bozzolo, Lucrezia Rovati, Paolo Giorgio Arcidiacono, Gianpaolo Balzano, Dejan Lazarevic, Chiara Bonini, Massimo Falconi, John H Stone, Lorenzo Dagna, Shiv Pillai, Angelo A Manfredi
OBJECTIVE: An unconventional population of CD4+ SLAMF7+ cytotoxic TEM cells (CD4+ CTLs) has been linked causally to IgG4-related disease (IgG4-RD). Glucocorticoids represent the first line therapeutic approach in patients with IgG4-RD but their mechanism of action in this specific condition remains unknown. Here we describe the impact of glucocorticoids on CD4+ CTLs in IgG4-RD. METHODS: CD8α, granzyme A, perforin, and SLAMF7 expression within the effector/memory compartment of CD45RO (TEM ) and CD45RA (TEMRA ) CD4+ T cells was quantified by flow cytometry in 18 active IgG4-RD patients at baseline and after 6 months of glucocorticoid treatment...
March 2, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#7
REVIEW
Jill M Comeau, Katherine Kelly, Gary W Jean
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy and safety, cost, and place in therapy of elotuzumab for treatment of relapsed or refractory multiple myeloma (MM) are reviewed. SUMMARY: Elotuzumab is a humanized monoclonal antibody that targets the signaling lymphocytic activation molecule (SLAM) protein SLAMF7 and facilitates an antibody-dependent cellular cytotoxicity interaction between myeloma cells and natural killer cells. Elotuzumab has U.S...
January 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29296719/pd-1-blockade-enhances-elotuzumab-efficacy-in-mouse-tumor-models
#8
Natalie A Bezman, Amy Jhatakia, Alper Y Kearney, Ty Brender, Mark Maurer, Karla Henning, Misty R Jenkins, Amy J Rogers, Paul J Neeson, Alan J Korman, Michael D Robbins, Robert F Graziano
Elotuzumab, a humanized monoclonal antibody that binds human signaling lymphocytic activation molecule F7 (hSLAMF7) on myeloma cells, was developed to treat patients with multiple myeloma (MM). Elotuzumab has a dual mechanism of action that includes the direct activation of natural killer (NK) cells and the induction of NK cell-mediated antibody-dependent cellular cytotoxicity. This study aimed to characterize the effects of elotuzumab on NK cells in vitro and in patients with MM and to determine whether elotuzumab antitumor activity was improved by programmed death receptor-1 (PD-1) blockade...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#9
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
March 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29089311/slamf7-car-t-cells-eliminate-myeloma-and-confer-selective-fratricide-of-slamf7-normal-lymphocytes
#10
Tea Gogishvili, Sophia Danhof, Sabrina Prommersberger, Julian Rydzek, Martin Schreder, Christian Brede, Hermann Einsele, Michael Hudecek
SLAMF7 is under intense investigation as a target for immunotherapy in multiple myeloma. In this study, we redirected the specificity of T cells to SLAMF7 through expression of a chimeric antigen receptor (CAR) derived from the huLuc63 antibody (elotuzumab) and demonstrate that SLAMF7-CAR T cells prepared from patients and healthy donors confer potent antimyeloma reactivity. We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received previous treatment with proteasome inhibitors and immunomodulatory drugs...
December 28, 2017: Blood
https://www.readbyqxmd.com/read/29020082/expression-patterns-of-signaling-lymphocytic-activation-molecule-family-members-in-peripheral-blood-mononuclear-cell-subsets-in-patients-with-systemic-lupus-erythematosus
#11
Maria P Karampetsou, Denis Comte, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#12
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#13
REVIEW
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM...
December 14, 2017: Blood
https://www.readbyqxmd.com/read/28883263/combination-therapy-with-monoclonal-antibodies-for-treatment-of-newly-diagnosed-multiple-myeloma
#14
Noriko Nishimura, Yasuhito Terui, Kiyohiko Hatake
Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28861320/cs1-slamf7-cd319-is-an-effective-immunotherapeutic-target-for-multiple-myeloma
#15
REVIEW
Joseph D Malaer, Porunelloor A Mathew
CS1 (also known as CD319, CRACC and SLAMF7) was identified as an NK cell receptor regulating immune functions. It is also expressed on B cells, T cells, Dendritic cells, NK-T cells, and monocytes. CS1 is overexpressed in multiple myeloma and makes it a target for immunotherapy. A humanized anti-CS1 antibody, Elotuzumab or Empliciti has shown promising results in clinical studies. This review focuses on the biology of CS1 in NK and other hematopoietic cells and multiple myeloma. Anti-CS1 mAb can activate natural cytotoxicity of NK cells as well as enhance ADCC (antibody-dependent cell-mediated cytotoxicity) and thus makes an effective target for immunotherapy of MM...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28782413/coexistence-of-leishmaniasis-and-multiple-myeloma-in-the-era-of-monoclonal-antibody-anti-cd38-or-anti-slamf7-containing-triplets-one-shared-story-of-two-exceptional-cases
#16
Dimitrios C Ziogas, Evangelos Terpos, Maria Gavriatopoulou, Magdalini Migkou, Despoina Fotiou, Maria Roussou, Nikolaos Kanellias, Ioanna Tatouli, Evangelos Eleutherakis-Papaiakovou, Ioannis Panagiotidis, Ioannis Ntanasis-Stathopoulos, Efstathios Kastritis, Meletios A Dimopoulos
No abstract text is available yet for this article.
April 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28744161/emerging-combination-therapies-for-the-management-of-multiple-myeloma-the-role-of-elotuzumab
#17
REVIEW
Wei-Chih Chen, Abraham S Kanate, Michael Craig, William P Petros, Lori A Hazlehurst
Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#18
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28678593/neighborhood-characteristics-influence-dna-methylation-of-genes-involved-in-stress-response-and-inflammation-the-multi-ethnic-study-of-atherosclerosis
#19
Jennifer A Smith, Wei Zhao, Xu Wang, Scott M Ratliff, Bhramar Mukherjee, Sharon L R Kardia, Yongmei Liu, Ava V Diez Roux, Belinda L Needham
Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between 2 neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults...
August 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#20
REVIEW
Madhav V Dhodapkar, Ivan Borrello, Adam D Cohen, Edward A Stadtmauer
Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM...
2017: American Society of Clinical Oncology Educational Book
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