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antibody multiple myeloma

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https://www.readbyqxmd.com/read/28314721/t-cell-bispecific-antibodies-suppress-multiple-myeloma
#1
(no author information available yet)
T-cell bispecific antibodies (TCB) targeting BCMA or FcRH5 induce T cell-mediated myeloma cell death.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28303902/ms4a4a-a-novel-cell-surface-marker-for-m2-macrophages-and-plasma-cells
#2
Ratna Sanyal, Maria J Polyak, Jonathan Zuccolo, Mandip Puri, Lili Deng, Luc Roberts, Ania Zuba, Jan Storek, Joanne M Luider, Ellen M Sundberg, Adnan Mansoor, Eva Baigorri, Michael P Chu, Andrew R Belch, Linda M Pilarski, Julie P Deans
MS4A4A is a member of the membrane-spanning, 4 domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes...
March 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28292432/antibodies-create-killer-bonds-in-myeloma
#3
Marta Chesi, Rafael Fonseca
In this issue of Cancer Cell, Li et al. and Seckinger et al. describe promising results of two T-cell-dependent bi-specific antibodies for the treatment of multiple myeloma: one targets FcRH5 expressed on B cells, whereas the other targets the B cell maturation antigen expressed on plasma cells.
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28275090/how-i-manage-the-toxicities-of-myeloma-drugs
#4
Michel Delforge, Heinz Ludwig
The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first-and second-generation proteasome inhibitors, immunomodulatory agents and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti-myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrants a heightened vigilance for early and late side-effects, a priori because real-life patients can be more frail or present with one or more comorbidities...
March 8, 2017: Blood
https://www.readbyqxmd.com/read/28270081/tocilizumab-labeling-with-99mtechnetium-via-hynic-as-a-molecular-diagnostic-agent-for-multiple-myeloma
#5
Ximena Camacho, Camila Longo Machado, Maria Fernanda García, Marcelo Fernández, Natalia Oddone, Juan Benech, Juan Pablo Gambini, Hugo Cerecetto, Roger Chammas, Pablo Cabral, Eloisa Riva
BACKGROUND: Multiple myeloma (MM) incidence and mortality is increasing worldwide. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. OBJECTIVE: To radiolabel Tocilizumab with 99mTechnetium as a potential imaging agents for MM. METHODS: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S)...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28264055/enhancement-of-pomalidomide-anti-tumor-response-with-acy-241-a-selective-hdac6-inhibitor
#6
Brian J North, Ingrid Almeciga-Pinto, David Tamang, Min Yang, Simon S Jones, Steven N Quayle
Thalidomide-based Immunomodulatory Drugs (IMiDs®), including lenalidomide and pomalidomide, are effective therapeutics for multiple myeloma. These agents have been approved with, or are under clinical development with, other targeted therapies including proteasome inhibitors, αCD38 monoclonal antibodies, as well as histone deacetylase (HDAC) inhibitors for combination therapy. HDAC inhibitors broadly targeting Class I and IIb HDACs have shown potent preclinical efficacy but have frequently demonstrated an undesirable safety profile in combination therapy approaches in clinical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28262555/membrane-proximal-epitope-facilitates-efficient-t-cell-synapse-formation-by-anti-fcrh5-cd3-and-is-a-requirement-for-myeloma-cell-killing
#7
Ji Li, Nicola J Stagg, Jennifer Johnston, Michael J Harris, Sam A Menzies, Danielle DiCara, Vanessa Clark, Maria Hristopoulos, Ryan Cook, Dionysos Slaga, Rin Nakamura, Luke McCarty, Siddharth Sukumaran, Elizabeth Luis, Zhengmao Ye, Thomas D Wu, Teiko Sumiyoshi, Dimitry Danilenko, Genee Y Lee, Klara Totpal, Diego Ellerman, Isidro Hötzel, John R James, Teemu T Junttila
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys...
February 20, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28262554/target-expression-generation-preclinical-activity-and-pharmacokinetics-of-the-bcma-t-cell-bispecific-antibody-em801-for-multiple-myeloma-treatment
#8
Anja Seckinger, Jose Antonio Delgado, Samuel Moser, Laura Moreno, Brigitte Neuber, Anna Grab, Susanne Lipp, Juana Merino, Felipe Prosper, Martina Emde, Camille Delon, Melanie Latzko, Reto Gianotti, Remo Lüoend, Ramona Murr, Ralf J Hosse, Lydia Jasmin Harnisch, Marina Bacac, Tanja Fauti, Christian Klein, Aintzane Zabaleta, Jens Hillengass, Elisabetta Ada Cavalcanti-Adam, Anthony D Ho, Michael Hundemer, Jesus F San Miguel, Klaus Strein, Pablo Umaña, Dirk Hose, Bruno Paiva, Minh Diem Vu
We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3(+) T cell/myeloma cell crosslinking, followed by CD4(+)/CD8(+) T cell activation, and secretion of interferon-γ, granzyme B, and perforin. This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA(+) cells in cynomolgus monkeys...
February 27, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#9
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28249894/targeting-cd38-suppresses-induction-and-function-of-t-regulatory-cells-to-mitigate-immunosuppression-in-multiple-myeloma
#10
Xiaoyan Feng, Li Zhang, Chirag Acharya, Gang An, Kenneth Wen, Luqui Qiu, Nikhil C Munshi, Yu-Tzu Tai, Kenneth C Anderson
PURPOSE: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ Tregs and further define immune modulating effects of a therapeutic CD38 monoclonal antibody (mAb) Isatuximab (Isa)/SAR650984 in multiple myeloma (MM). EXPERIMENTAL DESIGN: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and MM patients. PBMCs were then treated with Isa with or without Lenalidomide (Len) or Pomalidomide (Pom) to identify their impact on percentage and immunosuppressive activity of Tregs on CD4+CD25- T cells (Tcons)...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213943/a-phase-2-safety-study-of-accelerated-elotuzumab-infusion-over-less-than-1-hour-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma
#11
James Berenson, Robert Manges, Suprith Badarinath, Alan Cartmell, Kristi McIntyre, Roger Lyons, Wael Harb, Hesham Mohamed, Ali Nourbakhsh, Robert Rifkin
Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-hour infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM...
February 18, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28210004/monoclonal-antibody-therapy-in-multiple-myeloma
#12
REVIEW
C Touzeau, P Moreau, C Dumontet
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. Although previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM...
March 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#13
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203341/new-monoclonal-antibodies-on-the-horizon-in-multiple-myeloma
#14
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Across all cancers, monoclonal antibodies have emerged as a potential strategy for cancer therapy. Monoclonal antibodies target antigens expressed on the surface of cancer cells and accessory cells. This targeted approach uses the host's immune system to promote the killing of cancer cells. Multiple myeloma (MM) is the second most common hematologic malignancy that remains incurable in the majority of patients. The treatment of MM has evolved dramatically over the past decade and continues to evolve with the approval of four new drugs in 2015...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#15
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/28185460/-daratumumab-hope-for-myeloma-patients-a-challenge-for-clinical-laboratories
#16
T Jelínek, M Kořístka, Z Čermáková, R Hájek
Monoclonal antibodies represent a standard part in the treatment of oncologic patients, but their efficacy in multiple myeloma used to be unsatisfactory. Daratumumab monotherapy was approved by the American FDA in 2015, after unprecedented results were obtained in a heavily pre-treated group of patients. In 2016 daratumumab was approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of myeloma patients who have received at least one prior therapy.The toxicity of the drug is low, and is dominated by infusion-related reactions in more or less half of patients...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28162031/successful-treatment-of-refractory-systemic-lupus-erythematosus-using-proteasome-inhibitor-bortezomib-followed-by-belimumab-description-of-two-cases
#17
C Sjöwall, M Hjorth, P Eriksson
Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28158311/a-single-arm-open-label-phase-2-clinical-trial-evaluating-disease-response-following-treatment-with-bi-505-a-human-anti-intercellular-adhesion-molecule-1-monoclonal-antibody-in-patients-with-smoldering-multiple-myeloma
#18
Stina Wichert, Gunnar Juliusson, Åsa Johansson, Elisabeth Sonesson, Ingrid Teige, Anna Teige Wickenberg, Björn Frendeus, Magnus Korsgren, Markus Hansson
BACKGROUND: Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects...
2017: PloS One
https://www.readbyqxmd.com/read/28154173/autocrine-and-paracrine-interactions-between-multiple-myeloma-cells-and-bone-marrow-stromal-cells-by-growth-arrest-specific-gene-6-crosstalk-with-interleukin-6
#19
Miki Furukawa, Hiroshi Ohkawara, Kazuei Ogawa, Kazuhiko Ikeda, Koki Ueda, Akiko Shichishima-Nakamura, Emi Ito, Jun-Ichi Imai, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Satoshi Waguri, Takayuki Ikezoe, Yasuchika Takeishi
The pathogenesis of multiple myeloma (MM) has not yet been fully elucidated. Our microarray analysis and immunohistochemistry revealed significant upregulation of growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein with a structural homology with protein S, in bone marrow (BM) cells of MM patients. ELISA showed that the serum levels of soluble Gas6 were significantly increased in the MM patients when compared with healthy controls. Gas6 was overexpressed in the human CD138-positive MM cell line RPMI-8226...
January 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28151713/immune-therapies-in-multiple-myeloma
#20
EDITORIAL
Shaji K Kumar, Kenneth C Anderson
Treatment paradigms have changed rapidly for multiple myeloma, and immune therapies have taken center stage. Advances in therapies for myeloma have led to a dramatic improvement in the survival of patients with this incurable malignancy. The immune system is significantly impaired in patients with myeloma as a result of the disease leading to suppression of normal plasma cells as well the negative effects on cellular immunity. Given this scenario, immune approaches have not been successful until recently. Monoclonal antibodies directed against CD38 (daratumumab) and SLAMF7 (elotuzumab) are already in the clinic, and several other antibodies directed against different plasma cell antigens are under evaluation...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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