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antibody multiple myeloma

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https://www.readbyqxmd.com/read/29788798/optimizing-therapy-in-bortezomib-exposed-patients-with-multiple-myeloma
#1
Magdalini Migkou, Maria Gavriatopoulou, Evangelos Terpos, Meletios Athanasios Dimopoulos
Multiple myeloma prognosis has improved significantly during the past decade, with survival prolongation mainly due to the incorporation of novel agents. Bortezomib represents one of the main backbone agents of antimyeloma treatment. Areas Covered: This review aims to identify possible and available therapeutic options for patients who experience disease refractoriness following bortezomib exposure. Expert Commentary: For patients who finally relapse after bortezomib exposure treatment strategy should be individualized...
May 23, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29784015/induction-of-multiple-myeloma-cancer-stem-cell-apoptosis-using-conjugated-anti-abcg2-antibody-with-epirubicin-loaded-microbubbles
#2
Fangfang Shi, Miao Li, Jing Wang, Di Wu, Meng Pan, Mei Guo, Jun Dou
BACKGROUND: Multiple myeloma (MM) currently remains largely incurable. Cancer stem cells (CSCs) are believed to be responsible for drug resistance and eventual relapse. In this study, we exploited a novel agent to evaluate its inhibitory effect on MM CSCs. METHODS: Epirubicin (EPI)-loaded lipid microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (EPI-MBs + mAb) were developed and their effect on MM 138- CD34- CSCs isolated from human MM RPMI 8226 cell line plus ultrasound exposure in vitro and in vivo in a nonobese diabetic/severe combined immunodeficient mouse model were assessed...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29769244/a-cs1-nkg2d-bispecific-antibody-collectively-activates-cytolytic-immune-cells-against-multiple-myeloma
#3
Wing Keung Chan, Siwen Kang, Youssef Youssef, Erin N Glankler, Emma R Barrett, Alex M Carter, Elshafa H Ahmed, Aman Prasad, Luxi Chen, Jianying Zhang, Don M Benson, Michael A Caligiuri, Jianhua Yu
Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb)...
May 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29768934/a-safety-profile-of-medications-used-to-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#4
Ramón García-Sanz, Cristina Jiménez, Verónica González de la Calle, María Eugenia Sarasquete
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the BTK inhibitors. Areas covered. Two main therapeutic attitudes are possible: 1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies, or; 2) new approaches with BTK inhibitors, usually alone...
May 17, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29759149/functional-imaging-methods-for-assessment-of-minimal-residual-disease-in-multiple-myeloma-current-status-and-novel-immunopet-based-methods
#5
REVIEW
Neeta Pandit-Taskar
Imaging plays a key role in assessment of myeloma. Osteolytic bone lesions are optimally assessed using structural imaging, however the structural changes lag the functional changes in the disease. Functional imaging with fluoro deoxy glucose (FDG) positron emission tomography (PET) computerized tomography (CT) is useful in assessment of high-risk myeloma. FDG PET provides prognostic information and is helpful in monitoring response to therapy. However, it is nonspecific and may not be optimal in assessing treatment response to immunotherapeutic agents...
January 2018: Seminars in Hematology
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#6
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/29748955/investigational-agents-in-immunotherapy-a-new-horizon-for-the-treatment-of-multiple-myeloma
#7
REVIEW
Cindy Varga, Jacob P Laubach, Kenneth C Anderson, Paul G Richardson
The treatment of multiple myeloma (MM) has gone through several major advances over the last 5 years with the introduction of next generation proteasome inhibitors (PI; carfilzomib, ixazomib) and immunomodulatory derivatives (IMiD; pomalidomide), with these new agents having a substantial impact on patient outcome. However, despite these advances, MM remains a highly resistant disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment...
May 10, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29741423/propensity-score-matching-analysis-to-evaluate-the-comparative-effectiveness-of-daratumumab-versus-real-world-standard-of-care-therapies-for-patients-with-heavily-pretreated-and-refractory-multiple-myeloma
#8
Shaji Kumar, Brian Durie, Hareth Nahi, Ravi Vij, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos, Xavier Leleu, Meral Beksac, Hartmut Goldschmidt, Jens Hillengass, Zhuo Su, Brian Hutton, Chris Cameron, Imran Khan, Annette Lam
Daratumumab is a CD38-directed monoclonal antibody approved for treating multiple myeloma (MM). Propensity score matching (PSM) based on individual patient data (IPD) was conducted to compare overall survival (OS) and progression-free survival (PFS) for daratumumab versus real-world standard of care (SOC). IPD for patients with relapsed and refractory (RR) MM treated with daratumumab monotherapy were from the GEN501 and SIRIUS studies; IPD for patients treated with SOC were from an International Myeloma Working Group (IMWG) chart review of patients with RRMM...
May 9, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29733502/natural-killer-cell-immunotherapy-against-multiple-myeloma-progress-and-possibilities
#9
REVIEW
Pan Liu, Yanxia Jin, Haseeb Sattar, Hailing Liu, Weiling Xie, Fuling Zhou
Multiple myeloma (MM) is a complex aggressive mature B-cell malignancy. Although with the wide application of chemotherapy drugs, it remains incurable and the vast majority of patients relapse. Natural killer (NK) cells, also known as CD56+ CD3- large granular lymphocytes, are cytotoxic innate immune cells against MM without prior sensitization steps. NK cell-based immunotherapy is extensively promising in a wide range of clinical settings. It is worthy of note that some novel drugs such as monoclonal antibodies (mAbs), proteasome inhibitors (PIs), and immunomodulators (IMiDs) directly or indirectly activate NK cells to enhance their antitumor activity, and the combined regimens significantly improve the prognosis of MM patients...
May 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29709247/blocking-don-t-eat-me-signal-of-cd47-sirp%C3%AE-in-hematological-malignancies-an-in-depth-review
#10
REVIEW
Atlantis Russ, Anh B Hua, William R Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S Carew, Steffan T Nawrocki, Daniel Persky, Faiz Anwer
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148...
April 14, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29706958/one-year-follow-up-of-natural-killer-cell-activity-in-multiple-myeloma-patients-treated-with-adjuvant-lenalidomide-therapy
#11
Laurie Besson, Emily Charrier, Lionel Karlin, Omran Allatif, Antoine Marçais, Paul Rouzaire, Lucie Belmont, Michel Attal, Christine Lombard, Gilles Salles, Thierry Walzer, Sébastien Viel
Multiple myeloma (MM) is a proliferation of tumoral plasma B cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro and can limit MM growth in vivo . Previous reports have shown that NK cell function is impaired during MM progression and suggested that treatment with immunomodulatory drugs (IMIDs) such as lenalidomide (LEN) could enhance it. However, the effects of IMIDs on NK cells have been tested mostly in vitro or in preclinical models and supporting evidence of their effect in vivo in patients is lacking...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29702149/the-link-between-bone-microenvironment-and-immune-cells-in-multiple-myeloma-emerging-role-of-cd38
#12
REVIEW
Marina Bolzoni, Denise Toscani, Federica Costa, Emanuela Vicario, Franco Aversa, Nicola Giuliani
The relationship between bone and immune cells is well established both in physiological and pathological conditions. Multiple myeloma (MM) is a plasma cell malignancy characterized by an increase of number and activity of osteoclasts (OCLs) and a decrease of osteoblasts (OBs). These events are responsible for bone lesions of MM patients. OCLs support MM cells survival in vitro and in vivo. Recently, the possible role of OCLs as immunosuppressive cells in the MM BM microenvironment has been underlined. OCLs protect MM cells against T cell-mediated cytotoxicity through the expression of several molecules including programmed death-ligand (PD-L) 1, galectin (Gal) 9, CD200, and indoleamine-2,3-dioxygenase (IDO)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29702148/immunomodulatory-effects-of-cd38-targeting-antibodies
#13
REVIEW
Niels W C J van de Donk
The fist in class CD38-targeting antibody, daratumumab, is currently approved as single agent and in combination with standards of care for the treatment of relapsed and refractory multiple myeloma. Based on the high activity and favorable toxicity profile of daratumumab, other CD38 antibodies, such as isatuximab, MOR202, and TAK-079, are being evaluated in MM and other malignancies. The CD38-targeting antibodies have classic Fc-dependent immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29701218/synthesis-of-c-functionalized-te1pa-and-comparison-with-its-analogues-an-example-of-bioconjugation-on-9e7-4-mab-for-multiple-myeloma-64-cu-pet-imaging
#14
Thomas Le Bihan, Anne-Sophie Navarro, Nathalie Le Bris, Patricia Le Saëc, Sébastien Gouard, Ferid Haddad, Jean-François Gestin, Michel Chérel, Alain Faivre-Chauvet, Raphaël Tripier
In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized...
April 27, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29701006/nanotherapeutics-for-multiple-myeloma
#15
REVIEW
Alexander Zheleznyak, Monica Shokeen, Samuel Achilefu
Multiple myeloma (MM) is an age-related hematological malignancy with an estimated 30,000 new cases and 13,000 deaths per year. A disease of antibody-secreting malignant plasma B-cells that grow primarily in the bone marrow (BM), MM causes debilitating fractures, anemia, renal failure, and hypercalcemia. In addition to the abnormal genetic profile of MM cells, the permissive BM microenvironment (BMM) supports MM pathogenesis. Although advances in treatment options have significantly enhanced survival in MM patients, transient perfusion of small-molecule drugs in the BM does not provide sufficient residence to enhance MM cell-drug interaction, thus allowing some myeloma cells to escape the first line of treatment...
April 26, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29700211/monoclonal-antibodies-and-multiple-myeloma-all-in-all-it-s-just-another-brick-in-the-wall
#16
Pellegrino Musto
No abstract text is available yet for this article.
April 26, 2018: Oncologist
https://www.readbyqxmd.com/read/29696629/current-use-of-monoclonal-antibodies-in-the-treatment-of-multiple-myeloma
#17
REVIEW
Cindy Varga, Michelle Maglio, Irene M Ghobrial, Paul G Richardson
Multiple myeloma (MM) is the second most common haematological malignancy after non-Hodgkin lymphoma. Despite the improvement in outcomes over the last decade with the introduction of novel therapies, such as immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), MM remains an incurable disease. Patients who are both refractory to IMiDs and PIs carry a particularly dismal prognosis. The development of targeted therapy in the form of monoclonal antibodies has shifted the treatment paradigm of this disease, resulting in unprecedented response rates, even among the highest-risk patients...
April 25, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29666962/activity-of-indatuximab-ravtansine-against-triple-negative-breast-cancer-in-preclinical-tumor-models
#18
Kurt Schönfeld, Peter Herbener, Chantal Zuber, Thomas Häder, Katrin Bernöster, Christoph Uherek, Jörg Schüttrumpf
PURPOSE: Triple-negative breast cancer (TNBC) is related with a poor prognosis as patients do hardly benefit from approved therapies. CD138 (Syndecan-1) is upregulated on human breast cancers. Indatuximab ravtansine (BT062) is an antibody-drug-conjugate that specifically targets CD138-expressing cells and has previously shown clinical activity in multiple myeloma. Here we show indatuximab ravtansine as a potential mono- and combination therapy for TNBC. METHODS: The effects of indatuximab ravtansine were assessed in vitro in SK-BR-3 and T47D breast cancer cell lines...
April 17, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29666301/fratricide-of-nk-cells-in-daratumumab-therapy-for-multiple-myeloma-overcome-by-ex-vivo-expanded-autologous-nk-cells
#19
Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A Caligiuri, Don M Benson, Jianhua Yu
PURPOSE: Daratumumab and its use in combination with other agents is becoming a new standard of care for treatment of multiple myeloma (MM). We mechanistically studied how daratumumab acts on NK cells. EXPERIMENTAL DESIGN: Quantities of NK cells in peripheral blood (PB) and/or bone marrow (BM) of MM patients or healthy donors were examined by flow cytometry. NK cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661776/targeting-the-leukemia-antigen-pr1-with-immunotherapy-for-the-treatment-of-multiple-myeloma
#20
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca S Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda C Herrmann, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
PURPOSE: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. Since multiple myeloma (MM) is derived from B cells, we investigated whether MM is also capable of PR1 cross-presentation and subsequently capable of being targeted using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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