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https://www.readbyqxmd.com/read/29368256/immunopathogenesis-and-immunotherapy-of-multiple-myeloma
#1
REVIEW
Hideto Tamura
Despite the advent of novel therapies and improvements in survival, multiple myeloma (MM) remains an incurable disease. Thus, new treatment strategies including immunotherapies are needed for MM patients with stable disease after induction chemotherapy as well as for disease control in patients with advanced disease. However, profound immune dysregulation not only of B cells, but also of other immune cells such as natural killer cells, T cells, and dendritic cells and increase in the number of immunosuppressive cells, i...
January 24, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#2
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/29296857/effects-of-daratumumab-on-natural-killer-cells-and-impact-on-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#3
Tineke Casneuf, Xu Steven Xu, Homer C Adams, Amy E Axel, Christopher Chiu, Imran Khan, Tahamtan Ahmadi, Xiaoyu Yan, Sagar Lonial, Torben Plesner, Henk M Lokhorst, Niels W C J van de Donk, Pamela L Clemens, A Kate Sasser
Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy and safety, were assessed...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296719/pd-1-blockade-enhances-elotuzumab-efficacy-in-mouse-tumor-models
#4
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/29163516/restoring-natural-killer-cell-immunity-against-multiple-myeloma-in-the-era-of-new-drugs
#5
REVIEW
Gianfranco Pittari, Luca Vago, Moreno Festuccia, Chiara Bonini, Deena Mudawi, Luisa Giaccone, Benedetto Bruno
Transformed plasma cells in multiple myeloma (MM) are susceptible to natural killer (NK) cell-mediated killing via engagement of tumor ligands for NK activating receptors or "missing-self" recognition. Similar to other cancers, MM targets may elude NK cell immunosurveillance by reprogramming tumor microenvironment and editing cell surface antigen repertoire. Along disease continuum, these effects collectively result in a progressive decline of NK cell immunity, a phenomenon increasingly recognized as a critical determinant of MM progression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29091475/a-review-discussing-elotuzumab-and-its-use-in-the-second-line-plus-treatment-of-multiple-myeloma
#6
Massimo Offidani, Laura Corvatta
Monoclonal antibodies (mAb) represent a new frontier to treat newly diagnosed and relapsed-refractory multiple myeloma (MM). Elotuzumab, an mAb targeted SLAM7 in the plasma cells and natural killer cells surface, is the first mAb approved for the treatment of relapsed-refractory MM in combination with lenalidomide and dexamethasone. This approval was the final result of several preclinical and Phase I-II clinical studies leading to ELOQUENT-2 Phase III trial that demonstrated that elotuzumab adds a significant and durable value to standard therapy, paved the way of this new treatment strategy for MM...
November 1, 2017: Future Oncology
https://www.readbyqxmd.com/read/29061445/amelioration-of-nk-cell-function-driven-by-v%C3%AE-24-invariant-nkt-cell-activation-in-multiple-myeloma
#7
Tomonori Iyoda, Satoru Yamasaki, Michihiro Hidaka, Fumio Kawano, Yu Abe, Kenshi Suzuki, Norimitsu Kadowaki, Kanako Shimizu, Shin-Ichiro Fujii
NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells...
October 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#8
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28874810/innate-immune-activating-ligand-sumoylation-affects-tumor-cell-recognition-by-nk-cells
#9
Beatrice Zitti, Rosa Molfetta, Cinzia Fionda, Linda Quatrini, Helena Stabile, Mario Lecce, Valeria de Turris, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Marco Cippitelli, Angela Gismondi, Angela Santoni, Rossella Paolini
Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744161/emerging-combination-therapies-for-the-management-of-multiple-myeloma-the-role-of-elotuzumab
#10
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
#11
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/28620928/the-importance-of-the-number-of-transplanted-cells-with-dipeptidyl-peptidase-4-expression-on-the-haematopoietic-recovery-and-lymphocyte-reconstitution-in-patients-with-multiple-myeloma-after-autologous-haematopoietic-stem-cell-transplantation
#12
Anna Kopinska, Małgorzata Krawczyk-Kulis, Joanna Dziaczkowska-Suszek, Katarzyna Bieszczad, Krystyna Jagoda, Slawomira Kyrcz-Krzemien
Autologous haematopoietic stem cell transplantation (AHSCT) remains recommended treatment in the first remission in multiple myeloma (MM). In earlier research it has been suggested that there is an influence of the expression of dipeptidyl peptidase-4 (CD26) on both the homing and lymphocyte reconstitution after AHSCT. The aim of the study is to investigate the influence of transplanted cells CD26+ on the haematopoietic recovery and lymphocyte reconstitution after AHSCT in MM. Forty eight patients with MM underwent AHSCT in our centre...
June 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#13
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28385777/both-mucosal-associated-invariant-and-natural-killer-t-cell-deficiency-in-multiple-myeloma-can-be-countered-by-pd-1-inhibition
#14
LETTER
Mérédis Favreau, Koen Venken, Sylvia Faict, Ken Maes, Kim De Veirman, Elke De Bruyne, Xavier Leleu, Louis Boon, Dirk Elewaut, Karin Vanderkerken, Eline Menu
No abstract text is available yet for this article.
July 2017: Haematologica
https://www.readbyqxmd.com/read/28295190/phase-i-study-of-cord-blood-derived-natural-killer-cells-combined-with-autologous-stem-cell-transplantation-in-multiple-myeloma
#15
Nina Shah, Li Li, Jessica McCarty, Indreshpal Kaur, Eric Yvon, Hila Shaim, Muharrem Muftuoglu, Enli Liu, Robert Z Orlowski, Laurence Cooper, Dean Lee, Simrit Parmar, Kai Cao, Catherine Sobieiski, Rima Saliba, Chitra Hosing, Sairah Ahmed, Yago Nieto, Qaiser Bashir, Krina Patel, Catherine Bollard, Muzaffar Qazilbash, Richard Champlin, Katy Rezvani, Elizabeth J Shpall
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2 on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 CB-NK cells/kg...
May 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28278706/high-expression-levels-of-ip10-cxcl10-are-associated-with-modulation-of-the-natural-killer-cell-compartment-in-multiple-myeloma
#16
Giovanni Bernardini, Elisabetta Vulpis, Valentina Bonanni, Helena Stabile, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Angela Gismondi, Angela Santoni, Alessandra Zingoni
No abstract text is available yet for this article.
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28249894/targeting-cd38-suppresses-induction-and-function-of-t-regulatory-cells-to-mitigate-immunosuppression-in-multiple-myeloma
#17
Xiaoyan Feng, Li Zhang, Chirag Acharya, Gang An, Kenneth Wen, Lugui Qiu, Nikhil C Munshi, Yu-Tzu Tai, Kenneth C Anderson
Purpose: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ regulatory T cells (Treg) and further define immunomodulating effects of a therapeutic CD38 mAb isatuximab/SAR650984 in multiple myeloma.Experimental Design: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and multiple myeloma patients. Peripheral blood mononuclear cells (PBMC) were then treated with isatuximab with or without lenalidomide or pomalidomide to identify their impact on the percentage and immunosuppressive activity of Tregs on CD4+CD25- T cells (Tcons)...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#18
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#19
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/27992381/low-dose-bortezomib-increases-the-expression-of-nkg2d-and-dnam-1-ligands-and-enhances-induced-nk-and-%C3%AE-%C3%AE-t-cell-mediated-lysis-in-multiple-myeloma
#20
Chao Niu, Haofan Jin, Min Li, Shan Zhu, Lei Zhou, Feng Jin, Yulai Zhou, Dongsheng Xu, Jianting Xu, Lianjing Zhao, Shanshan Hao, Wei Li, Jiuwei Cui
Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) or γδ T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and γδ T cells further improves outcomes in MM, and how the treatments should be combined, remain unclear. Herein, we found that low-dose bortezomib did not suppress the viability of induced NK and γδ T cells, but did induce MM cell apoptosis...
January 24, 2017: Oncotarget
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