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natural killer cell myeloma

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https://www.readbyqxmd.com/read/28744161/emerging-combination-therapies-for-the-management-of-multiple-myeloma-the-role-of-elotuzumab
#1
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
#2
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
#3
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
#4
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
#5
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.
April 6, 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
#6
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/m(2) 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 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) 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
#7
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
#8
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(+)CD25(high)Foxp3(+) 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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27904448/mobilization-with-cyclophosphamide-reduces-the-number-of-lymphocyte-subpopulations-in-the-leukapheresis-product-and-delays-their-reconstitution-after-autologous-hematopoietic-stem-cell-transplantation-in-patients-with-multiple-myeloma
#12
Matevz Skerget, Barbara Skopec, Darja Zontar, Peter Cernelc
BACKGROUND: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#13
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#14
REVIEW
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
January 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#15
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27848182/elotuzumab-with-lenalidomide-and-dexamethasone-for-japanese-patients-with-relapsed-refractory-multiple-myeloma-phase-1-study
#16
Shinsuke Iida, Hirokazu Nagai, Gen Kinoshita, Masafumi Miyoshi, Michael Robbins, Dimple Pandya, Eric Bleickardt, Takaaki Chou
Elotuzumab is an immunostimulatory monoclonal antibody that binds to SLAMF7, a type-1 transmembrane protein expressed on myeloma and natural killer cells. We report a phase 1 study (NCT01241292) in which we evaluated the safety, efficacy and pharmacokinetics of elotuzumab combined with lenalidomide and dexamethasone in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In 28-day cycles, patients received: elotuzumab (intravenously), lenalidomide (25 mg orally) and weekly dexamethasone (elotuzumab days: 28 mg orally plus 8 mg intravenously; non-elotuzumab days: 40 mg orally)...
March 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#17
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27785050/spotlight-on-elotuzumab-in-the-treatment-of-multiple-myeloma-the-evidence-to-date
#18
REVIEW
Katja Weisel
Despite advances in the treatment of multiple myeloma, it remains an incurable disease, with relapses and resistances frequently observed. Recently, immunotherapies, in particular, monoclonal antibodies, have become important treatment options in anticancer therapies. Elotuzumab is a humanized monoclonal antibody to signaling lymphocytic activation molecule F7, which is highly expressed on myeloma cells and, to a lower extent, on selected leukocyte subsets such as natural killer cells. By directly activating natural killer cells and by antibody-dependent cell-mediated cytotoxicity, elotuzumab exhibits a dual mechanism of action leading to myeloma cell death with minimal effects on normal tissue...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27696265/role-of-the-immune-response-in-disease-progression-and-therapy-in-multiple-myeloma
#19
REVIEW
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27695618/treatment-of-multiple-myeloma-with-the-immunostimulatory-slamf7-antibody-elotuzumab
#20
REVIEW
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
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