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Monoclonal antibody

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https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#1
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#2
Sheema Khan, Nadeem Zafar, Shabia S Khan, Saini Setua, Stephen W Behrman, Zachary E Stiles, Murali M Yallapu, Peeyush Sahay, Hemendra Ghimire, Tomoko Ise, Satoshi Nagata, Lei Wang, Jim Y Wan, Prabhakar Pradhan, Meena Jaggi, Subhash C Chauhan
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses...
January 15, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29351573/multicenter-french-harmonization-study-for-pd-l1-ihc-testing-in-non-small-cell-lung-cancer
#3
J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Background: Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351275/a-mathematical-model-for-il-6-mediated-stem-cell-driven-tumor-growth-and-targeted-treatment
#4
Fereshteh Nazari, Alexander T Pearson, Jacques Eduardo Nör, Trachette L Jackson
Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#5
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29350565/safety-and-efficacy-of-denosumab-in-osteoporotic-patients-previously-treated-with-other-medications-a-systematic-review-and-meta-analysis
#6
Andreas Fontalis, Kenanidis Eustathios, Efthymia Prousali, Potoupnis Michael, Tsiridis Eleftherios
Denosumab is a monoclonal antibody that received approval by the FDA for the treatment of osteoporosis in 2010. Available higher level research evidence concerns the treatment of patients that have not received any anti-osteoporotic medication in the past. Further investigation is warranted, since clinicians often face the challenge of administering the most efficacious drug in patients, pretreated with other medications. Areas Covered: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of denosumab compared to other active anti-osteoporotic agents in patients formerly receiving other treatments...
January 19, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29350486/inflammatory-response-and-treatment-tolerance-of-long-term-infusion-of-the-anti-gd2-antibody-ch14-18-cho-in-combination-with-interleukin-2-in-patients-with-high-risk-neuroblastoma
#7
Kiraz Ceylan, Luciana J Jahns, Bjoern N Lode, Karoline Ehlert, Silke Kietz, Sascha Troschke-Meurer, Nikolai Siebert, Holger N Lode
BACKGROUND: The monoclonal anti-GD2 antibody ch14.18/CHO in combination with IL-2 is active and effective in high-risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long-term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m2 ; 24 hr) in combination with subcutaneous (s.c.) IL-2 in a single center program. METHODS: Fifty-three NB patients received up to six cycles of 100 mg/m2 ch14.18/CHO (d8-18, where d represents day(s)) as LTI combined with 6 × 106 IU/m2 s...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350441/ultrasensitive-detection-of-shiga-toxin-2-and-its-variants-in-shiga-toxin-producing-escherichia-coli-strains-by-a-time-resolved-fluorescence-immunoassay
#8
Tian Wen, Chao Huang, Yi Zhang, Xiaoyan Zeng, Wendong Liu, Zhenbang Jiao, Xiling Guo, Yongjun Jiao
A rapid and sensitive two-step time-resolved fluorescence immunoassay (TRFIA) was developed for the detection of Shiga toxin 2 (Stx2) and its variants in Shiga toxin-producing Escherichia coli (STEC) strains. In sandwich mode, a monoclonal antibody against Stx2 was coated on a microtiter plate as a capture antibody. A tracer antibody against Stx2 labeled with europium(III) (Eu3+ ) chelate was then used as a detector, followed by fluorescence measurements using time-resolved fluorescence. The sensitivity of Stx2 detection was 0...
January 19, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#9
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29349534/psoriasis-from-pathogenesis-to-targeted-therapies
#10
REVIEW
Curdin Conrad, Michel Gilliet
Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization...
January 18, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29348926/a-double-blind-placebo-controlled-single-ascending-dose-study-of-remyelinating-antibody-rhigm22-in-people-with-multiple-sclerosis
#11
Andrew Eisen, Benjamin M Greenberg, James D Bowen, Douglas L Arnold, Anthony O Caggiano
Objective: The objective of this paper is to assess, in individuals with clinically stable multiple sclerosis (MS), the safety, tolerability, pharmacokinetics (PK) and exploratory pharmacodynamics of the monoclonal recombinant human antibody IgM22 (rHIgM22). Methods: Seventy-two adults with stable MS were enrolled in a double-blind, randomized, placebo-controlled, single ascending-dose, Phase 1 trial examining rHIgM22 from 0.025 to 2.0 mg/kg. Assessments included MRI, MR spectroscopy, plasma PK, and changes in clinical status, laboratory values and adverse events for three months...
October 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29348674/variation-at-position-350-in-the-chikungunya-virus-6k-e1-protein-determines-the-sensitivity-of-detection-in-a-rapid-e1-antigen-test
#12
Aekkachai Tuekprakhon, Emi E Nakayama, Koen Bartholomeeusen, Orapim Puiprom, Tadahiro Sasaki, Ralph Huits, Natthanej Luplertlop, Nathamon Kosoltanapiwat, Pannamas Maneekan, Kevin K Ariën, Tatsuo Shioda, Pornsawan Leaungwutiwong
Chikungunya virus (CHIKV), a mosquito-borne pathogen, consists of three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. Although a current rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity to ECSA-genotype viruses, it showed poor performance against the Asian-genotype virus that is spreading in the American continents. To understand the basis for the low performance of this IC test against Asian-genotype virus, we re-examined the anti-CHIKV monoclonal antibodies (mAbs) used in the assay for their interaction with E1-antigen of the three CHIKV genotypes...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#13
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29347993/updated-efficacy-of-avelumab-in-patients-with-previously-treated-metastatic-merkel-cell-carcinoma-after-%C3%A2-1%C3%A2-year-of-follow-up-javelin-merkel-200-a-phase-2-clinical-trial
#14
Howard L Kaufman, Jeffery S Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Anja von Heydebreck, Meliessa Hennessy, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease...
January 19, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29347937/monoclonal-antibody-based-colloid-gold-immunochromatographic-strip-for-the-rapid-detection-of-tomato-zonate-spot-tospovirus
#15
Yanbing Niu, Defu Wang, Liyan Cui, Baoxia Wang, Xiaojing Pang, Peixia Yu
BACKGROUND: Tomato zonate spot virus (TZSV), a new species of genus Tospovirus, caused significant losses in yield and problems in quality of many important vegetables and ornamentals in Southwest China and posed a serious threat to important economic crops for the local farmers. A convenient and reliable method was urgently needed for rapid detection and surveillance of TZSV. METHODS: The nucleocapsid protein (N) of TZSV was expressed in Escherichia coli and purified, and was used as the antigen to immunize BALB/c mice...
January 18, 2018: Virology Journal
https://www.readbyqxmd.com/read/29347858/where-are-we-with-injectables-against-hiv-infection-and-what-are-the-remaining-challenges
#16
Said A Hassounah, Thibault Mesplède
Drug adherence has been a recurring issue in the field of HIV treatment, and low treatment adherence is typically associated with emergence of drug resistance, treatment failure and increased risks of transmission. Injectable antiretroviral drugs offer a unique opportunity to counter this issue for the treatment of HIV-positive individuals. In addition, injectables offer a remarkable opportunity to reduce new HIV infections, if applied in the context of both treatment-as-prevention and pre-exposure prophylaxis...
January 19, 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#17
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#18
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29345521/development-and-validation-of-an-elisa-to-study-panitumumab-pharmacokinetics
#19
Céline Desvignes, Christophe Passot, David Ternant, Morgane Caulet, Caroline Guérineau, Thierry Lecomte, Gilles Paintaud
AIM: Panitumumab is a monoclonal antibody directed against EGFR that is approved for the treatment of metastatic colorectal cancer. To investigate its pharmacokinetics and concentration-response relationship, a validated assay is required. RESULTS: An ELISA assay was developed and validated according to international recommendations. Six calibrators (ranging from 0.1 to 20 mg/l) plus one anchor point (50 mg/l) and three quality controls (0.45, 2 and 8 mg/l) were defined...
January 18, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29345354/lack-of-functional-selectin-ligand-interactions-enhances-innate-immune-resistance-to-systemic-listeria-monocytogenes-infection
#20
Gerard Agbayani, Komal Gurnani, Ahmed Zafer, Subash Sad, Lakshmi Krishnan
Selectin-ligand interactions are important for leukocyte homing and functionality. The roles of selectin-ligand interactions in modulating immunity to intracellular infections are not completely understood. Mice lacking the expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII double knockout, FtDKO) exhibit deficient functionality of selectin-ligand interactions. We addressed the kinetics of infection and immunity to Listeria monocytogenes (LM), an intracellular pathogen, in FtDKO mice...
December 27, 2017: Journal of Leukocyte Biology
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