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natural killer cell myeloma

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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
#1
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
#2
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
#3
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...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#4
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
#5
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)...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27634753/adoptive-transfer-of-tumor-specific-th2-cells-eradicates-tumors-by-triggering-an-in-situ-inflammatory-immune-response
#10
Kristina Berg Lorvik, Clara Hammarstrom, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma...
September 12, 2016: Cancer Research
https://www.readbyqxmd.com/read/27578390/plerixafor-as-preemptive-strategy-results-in-high-success-rates-in-autologous-stem-cell-mobilization-failure
#11
Nina Worel, Gerhard Fritsch, Hermine Agis, Alexandra Böhm, Georg Engelich, Gerda C Leitner, Klaus Geissler, Karoline Gleixner, Peter Kalhs, Veronika Buxhofer-Ausch, Felix Keil, Gerhard Kopetzky, Viktor Mayr, Werner Rabitsch, Regina Reisner, Konrad Rosskopf, Reinhard Ruckser, Claudia Zoghlami, Niklas Zojer, Hildegard T Greinix
Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2...
August 31, 2016: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/27498187/poly-phosphorhydrazone-dendrimers-yin-and-yang-of-monocyte-activation-for-human-nk-cell-amplification-applied-to-immunotherapy-against-multiple-myeloma
#12
Mary Poupot, Cédric-Olivier Turrin, Anne-Marie Caminade, Jean-Jacques Fournié, Michel Attal, Rémy Poupot, Séverine Fruchon
Human natural killer (NK) cells play a key role in anti-cancer and anti-viral immunity, but their selective amplification in vitro is extremely tedious to achieve and remains one of the most challenging problems to solve for efficient NK cell-based immuno-therapeutic treatments against malignant diseases. Here we report that, when added to ex vivo culture of peripheral blood mononuclear cells from healthy volunteers or from cancer patients with multiple myeloma, poly (phosphorhydrazone) dendrimers capped with amino-bis(methylene phosphonate) end groups enable the efficient proliferation of NK cells with anti-cancer cytotoxicity in vivo...
November 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27493711/a-comprehensive-review-of-lenalidomide-in-b-cell-non-hodgkin-lymphoma
#13
REVIEW
Mili Arora, Sonia Gowda, Joseph Tuscano
Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q- myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493709/elotuzumab-the-first-approved-monoclonal-antibody-for-multiple-myeloma-treatment
#14
REVIEW
Hila Magen, Eli Muchtar
Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27430580/targeting-kir-blockade-in-multiple-myeloma-trouble-in-checkpoint-paradise
#15
Martin Felices, Jeffrey S Miller
Findings within the current issue indicate that treatment with IPH2101 when used as monotherapy in smoldering multiple myeloma, meant to enhance natural killer cell function through inhibitory KIR blockade, results in a surprising reduction of NK cell function mediated through monocyte trogocytosis. The significance of these findings is discussed.
July 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27430430/increase-of-cik-cell-efficacy-by-upregulating-cell-surface-mica-and-inhibition-of-nkg2d-ligand-shedding-in-multiple-myeloma
#16
Chidimma A Nwangwu, Hans Weiher, Ingo G H Schmidt-Wolf
Multiple myeloma, which is a monoclonal plasma cell malignancy, still remains incurable despite recent progress in our understanding of this disorder. Adoptive immunotherapy of multiple myeloma using cytokine-induced killer cells is yielding promising results in clinical trials; however, some myeloma cells still evade immune surveillance by various unknown molecular mechanisms. This study aims at increasing the efficacy of cytokine-induced killer cells in targeting this tumor, using selective small-molecule inhibitors which increase and stabilize surface expression of the natural killer group 2, member D ligand, major histocompatibility complex class I polypeptide-related sequence A (MICA) on myeloma cells...
July 19, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27417553/elotuzumab-for-the-treatment-of-multiple-myeloma
#17
REVIEW
Yucai Wang, Larysa Sanchez, David S Siegel, Michael L Wang
Elotuzumab is one of the first two monoclonal antibodies that gained FDA approval for the treatment of multiple myeloma (MM). It targets SLAMF7, which is highly expressed in normal plasma and MM cells as well as natural killer (NK) cells. Elotuzumab demonstrated significant anti-myeloma activity in preclinical studies, and its mechanisms of action include mediating antibody-dependent cell-mediated cytotoxicity, enhancing cytotoxicity of NK cells, and inhibiting MM cell interaction with bone marrow stromal cells...
July 15, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27403737/trypanosoma-brucei-co-opts-nk-cells-to-kill-splenic-b2-b-cells
#18
Deborah Frenkel, Fengqiu Zhang, Patrick Guirnalda, Carole Haynes, Viki Bockstal, Magdalena Radwanska, Stefan Magez, Samuel J Black
After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/-) retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days...
July 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27356741/pd1-blockade-enhances-cytotoxicity-of-in-vitro-expanded-natural-killer-cells-towards-myeloma-cells
#19
Yanan Guo, Xiaoli Feng, Yang Jiang, Xiaoyun Shi, Xiangling Xing, Xiaoli Liu, Nailin Li, Bengt Fadeel, Chengyun Zheng
Aiming for an adoptive natural killer (NK) cell therapy, we have developed a novel protocol to expand NK cells from peripheral blood. With this protocol using anti-human CD16 antibody and interleukin (IL)-2, NK (CD3-CD56+) cells could be expanded about 4000-fold with over 70% purity during a 21-day culture. The expanded NK (exNK) cells were shown to be highly cytotoxic to multiple myeloma (MM) cells (RPMI8226) at low NK-target cell ratios. Furthermore, NK cells expanded in the presence of a blocking antibody (exNK+PD1-blockage) against programmed cell death protein-1 (PD1), a key counteracting molecule for NK and T cell activity, demonstrated more potent cytolytic activity against the RPMI8226 than the exNK cells without PD1 blocking...
June 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27342591/circulating-immune-cell-phenotype-can-predict-the-outcome-of-lenalidomide-plus-low-dose-dexamethasone-treatment-in-patients-with-refractory-relapsed-multiple-myeloma
#20
Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Tae Woo Kim, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Myungshin Kim, Chang-Ki Min
Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy...
August 2016: Cancer Immunology, Immunotherapy: CII
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