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https://www.readbyqxmd.com/read/30078440/car-t-cells-with-enhanced-sensitivity-to-b-cell-maturation-antigen-for-the-targeting-of-b-cell-non-hodgkin-s-lymphoma-and-multiple-myeloma
#1
Julia Bluhm, Elisa Kieback, Stephen F Marino, Felix Oden, Jörg Westermann, Markus Chmielewski, Hinrich Abken, Wolfgang Uckert, Uta E Höpken, Armin Rehm
Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and B cell non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted the B cell maturation antigen (BCMA), which is expressed in most cases of MM. We developed a humanized CAR with specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited a binding affinity in the low nanomolar range, conferring T cells with high functional avidity...
August 1, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30072119/shedding-of-baff-april-receptors-controls-b-cells
#2
Edgar Meinl, Franziska S Thaler, Stefan F Lichtenthaler
Proteolytic shedding of the receptors BCMA, TACI, and BAFFR reduces their cell-surface expression and ligand-mediated survival of B cell subsets. This shedding is executed by protease γ-secretase or by metalloproteases, and is partially dependent on ligand binding and receptor interactions. Shed receptors may serve as biomarkers for autoimmunity and lymphoma.
July 30, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/30053652/quantification-of-b-cell-maturation-antigen-a-target-for-novel-chimeric-antigen-receptor-t-cell-therapy-in-myeloma
#3
Dalia A Salem, Irina Maric, Constance M Yuan, David J Liewehr, David J Venzon, James Kochenderfer, Maryalice Stetler-Stevenson
B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and is targeted via anti-BCMA chimeric antigen receptor T-cell therapy (BCMA CAR T-cell therapy) in plasma cell myeloma (PCM) patients. Surface BCMA expression is required for CAR T-cell binding and killing. We determined the incidence and intensity of expression of BCMA in bone marrow PCM cells using flow cytometry (FC) and immunohistochemistry (IHC). PCM BCMA expression was assessed by FC in 70 patients and in 43 concurrent specimens by IHC...
August 2018: Leukemia Research
https://www.readbyqxmd.com/read/29909915/cars-and-other-t-cell-therapies-for-mm-the-clinical-experience
#4
REVIEW
Sophia Danhof, Michael Hudecek, Eric L Smith
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29908946/effects-of-cryopreservation-on-chimeric-antigen-receptor-t-cell-functions
#5
Hao Xu, Wenyue Cao, Liang Huang, Min Xiao, Yang Cao, Lei Zhao, Na Wang, Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved...
August 2018: Cryobiology
https://www.readbyqxmd.com/read/29899820/pre-clinical-validation-of-b-cell-maturation-antigen-bcma-as-a-target-for-t-cell-immunotherapy-of-multiple-myeloma
#6
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29877243/-multiple-myeloma-update-on-pathophysiology-and-management
#7
Ichiro Hanamura, Shinsuke Iida
Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-XL expression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29857405/exploring-nurses-perceptions-and-expectations-toward-a-bcma-implementation-using-a-mobile-app-and-workstations-as-a-change-management-strategy
#8
Liliana Giraldo, Bibiana Schachner, Daniel Luna, Sonia Benítez
The inclusion of new technologies in health, such as the 2D Codes scanning Drug Administration System (BCMA), has an impact on the perception of nurses, mainly changes in their workflow, and incorporation of mobile devices for patient care. The objective of this study is to know the perceptions and expectations of nurses regarding the implementation of BCMA. Qualitative research was conducted based on interviews with groups of nurses from different inpatient wards of the Hospital Italiano de Buenos Aires, with and without system implementation...
2018: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/29812997/t-cells-genetically-modified-to-express-an-anti-b-cell-maturation-antigen-chimeric-antigen-receptor-cause-remissions-of-poor-prognosis-relapsed-multiple-myeloma
#9
Jennifer N Brudno, Irina Maric, Steven D Hartman, Jeremy J Rose, Michael Wang, Norris Lam, Maryalice Stetler-Stevenson, Dalia Salem, Constance Yuan, Steven Pavletic, Jennifer A Kanakry, Syed Abbas Ali, Lekha Mikkilineni, Steven A Feldman, David F Stroncek, Brenna G Hansen, Judith Lawrence, Rashmika Patel, Frances Hakim, Ronald E Gress, James N Kochenderfer
Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients...
August 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29726440/nurses-attitude-for-using-barcode-medication-administration-system-in-a-developing-country
#10
Abbas Sheikhtaheri, Samane Saravani-Aval
Medication errors are common in healthcare settings. To prevent these errors, use of modern technology is suggested. Improvement of medication administration system particularly at the time of drug administration is mandated in Iran. Barcode medication administration (BCMA) systems are useful in this regard. This study was conducted to assess nurses' attitude for the use of BCMA systems. To this end, 283 randomly selected nurses working in teaching hospitals were surveyed using a five point Likert scale questionnaire...
2018: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/29678657/development-and-evaluation-of-an-optimal-human-single-chain-variable-fragment-derived-bcma-targeted-car-t-cell-vector
#11
Eric L Smith, Mette Staehr, Reed Masakayan, Ishan J Tatake, Terence J Purdon, Xiuyan Wang, Pei Wang, Hong Liu, Yiyang Xu, Sarah C Garrett-Thomson, Steven C Almo, Isabelle Riviere, Cheng Liu, Renier J Brentjens
B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered...
June 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29669947/anti-cd19-car-t-cells-with-high-dose-melphalan-and-autologous-stem-cell-transplantation-for-refractory-multiple-myeloma
#12
Alfred L Garfall, Edward A Stadtmauer, Wei-Ting Hwang, Simon F Lacey, Jan Joseph Melenhorst, Maria Krevvata, Martin P Carroll, William H Matsui, Qiuju Wang, Madhav V Dhodapkar, Kavita Dhodapkar, Rituparna Das, Dan T Vogl, Brendan M Weiss, Adam D Cohen, Patricia A Mangan, Emily C Ayers, Selene Nunez-Cruz, Irina Kulikovskaya, Megan M Davis, Anne Lamontagne, Karen Dengel, Naseem Ds Kerr, Regina M Young, Donald L Siegel, Bruce L Levine, Michael C Milone, Marcela V Maus, Carl H June
BACKGROUND: Multiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019). METHODS: Subjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29610956/prognostic-role-of-serial-quantitative-evaluation-of-18-f-fluorodeoxyglucose-uptake-by-pet-ct-in-patients-with-cardiac-sarcoidosis-presenting-with-ventricular-tachycardia
#13
Daniele Muser, Pasquale Santangeli, Simon A Castro, Jackson J Liang, Andres Enriquez, Thomas J Werner, Gaetano Nucifora, Silvia Magnani, Tatsuya Hayashi, Erica S Zado, Fermin C Garcia, David J Callans, Sanjay Dixit, Benoit Desjardins, Francis E Marchlinski, Abass Alavi
BACKGROUND: Positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) has shown to be useful in diagnosis, staging and monitoring of cardiac sarcoidosis (CS) but its interpretation is not standardized. OBJECTIVES: We sought to investigate the clinical impact of serial quantitative FDG uptake analysis in patients with CS presenting with ventricular tachycardia (VT) treated by catheter ablation (CA). METHODS: We followed 20 patients (51 ± 9 years, 70% males) with CS and VT who underwent CA, with 92 serial FDG-PET scans (3-10 per patient)...
July 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29590354/complex-automated-medication-systems-reduce-medication-administration-errors-in-a-danish-acute-medical-unit
#14
Bettina Wulff Risør, Marianne Lisby, Jan Sørensen
Objective: The objective of this study was to evaluate the effectiveness of two automated medication systems in reducing medication administration errors. Design: The study was a controlled before-and-after study and included three observation periods with collection of data during a 3-week period as initial baseline and two subsequent follow-up periods at 10 and 20 months. Setting: The study was conducted in two Danish acute medical units...
July 1, 2018: International Journal for Quality in Health Care
https://www.readbyqxmd.com/read/29576386/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2017
#15
REVIEW
Evangelos Terpos
The novel clinical data for myeloma that were presented in the 2017 Annual Meeting of the American Society of Hematology are summarized here. Studies with curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for patients with high-risk smoldering multiple myeloma (SMM) are described. Updated data from large phase III studies for patients with newly diagnosed MM (NDMM) who are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are described, along with the results of studies using novel anti-myeloma drug combinations for induction, consolidation, and maintenance as first-line therapy...
May 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29504446/the-clinical-significance-of-b-cell-maturation-antigen-as-a-therapeutic-target-and-biomarker
#16
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
April 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29421983/emerging-immune-targets-for-the-treatment-of-multiple-myeloma
#17
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29319682/bluebird-s-bcma-car-t-impresses-at-ash
#18
(no author information available yet)
No abstract text is available yet for this article.
January 10, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29319594/improving-bar-code-medication-administration-compliance-in-a-community-hospital-through-a-nursing-leadership-initiative
#19
Michael Van Ornum
Achieving optimal compliance for bar code medication administration (BCMA) in mature medication use systems is challenging due to the iterative system refinements over time. A nursing leadership initiative increased BCMA compliance, measured as a composite across all hospital units, from 95% to 98%, discovering unanticipated benefits and unintended consequences in the process. The methodology used provides valuable insight into effective strategies for BCMA optimization with applicability for other, similar quality improvement initiatives...
January 9, 2018: Journal of Nursing Care Quality
https://www.readbyqxmd.com/read/29312608/april-promotes-non-small-cell-lung-cancer-growth-and-metastasis-by-targeting-erk1-2-signaling
#20
Hengli Dou, Zhaohua Yan, Meng Zhang, Xiaoxin Xu
Non-small-cell lung cancer (NSCLC) is the major subtype of lung cancer, which is the most common cause of cancer-related mortality in the world. It is a complex disease involving multiple genetic alterations. As a cytokine belonging to the Tumor Necrosis Factor-α (TNF- α) family, the - a proliferation-inducing ligand (APRIL) expression and its signaling have been studied in many human solid tumor types, but the data on APRIL signaling in NSCLC are lacking. The aim of this study was to evaluate the APRIL expression and investigate its signaling in NSCLC...
December 12, 2017: Oncotarget
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