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monoclonal antibodies in therapy

Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Daniel Geh, Caroline Gordon
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE...
March 15, 2018: Expert Review of Clinical Immunology
Robert A Fenstermaker, Sheila A Figel, Jing-Xin Qiu, Tara A Barone, Sanam Sahjram Dharma, Evan K Winograd, Phillip M Galbo, Laura M Wiltsie, Michael J Ciesielski
PURPOSE: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in many cancers and represents an attractive molecule for targeted cancer therapy. Although primarily regarded as an intracellular protein with diverse actions, survivin has also been identified in association with circulating tumor exosomes. EXPERIMENTAL DESIGN: We have reported that active specific vaccination with a long peptide surviving immunogen leads to the development of survivin-specific CD8-mediated tumor cell lysis and prolongation of survival in tumor-bearing mice...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Carlos M Luna, Laura Pulido, Diego Burgos
PURPOSE OF REVIEW: As Streptococcus pneumoniae was considered the etiological agent of nearly all the cases of pneumonia at the beginning of the 20th century, and today is identified in fewer than 10-15% of cases, we analyze the possible causes of such a decline. RECENT FINDINGS: Extensive use of early empiric antimicrobial therapy, discovery of previously unrecognized pathogens, availability to newer diagnostic methods for the recognition of the pneumonia pathogens (PCR, urinary antigens, monoclonal antibodies etc...
March 13, 2018: Current Opinion in Pulmonary Medicine
Fabiola Fuchs, Martin Robausch
BACKGROUND: The topic of "medical oversupply at the end-of-life" is being discussed intensively internationally. The aim of this paper is to present the data of end-of-life care in one region in Austria (Lower Austria). METHODS: The data basis for the end-of-life indicators was the routine data (secondary data analysis) of the Lower Austrian District Health Insurance Fund (NÖGKK) from 2015. The basic population consisted of persons with inpatient hospitalization with a cancer diagnosis...
March 13, 2018: Wiener Medizinische Wochenschrift
Hongsik Cho, Byoung Ju Kim, Sang-Hyug Park, Karen A Hasty, Byoung-Hyun Min
Background: Early stage osteoarthritis (OA) is clinically asymptomatic due to the avascular and the aneural nature of the cartilage tissue. Nevertheless, early detection of cartilage tissue is critical in order to impede the progression of OA. Hence, in order to develop effective preventive therapy for OA, diagnosis in the early stages is necessary. Methods: To achieve this goal, we have developed targeted, fluorescent nanosomes conjugated with monoclonal anti-type II collagen antibodies (MabCII) for diagnosis of early OA...
2018: International Journal of Nanomedicine
Brunella Posteraro, Federico Pea, Luca Masucci, Patrizia Posteraro, Maurizio Sanguinetti
Clostridium difficile infection (CDI) is the most common healthcare-associated infection worldwide. As standard CDI antibiotic therapies can result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are necessary. A recently emerged immunological therapy is a monoclonal antibody against C. difficile toxin B. Areas covered: In this review, the authors summarize the available pharmacological, preclinical, and clinical data for the CDI treatment based on anti-toxin A (actoxumab) and anti-toxin B (bezlotoxumab) human monoclonal antibodies (HuMabs), and discuss about the potentiality of a therapy that includes HuMab combined administration for CDI...
March 15, 2018: Expert Opinion on Biological Therapy
Roberta Gualtierotti, Maria Orietta Borghi, Maria Gerosa, Tommaso Schioppo, Paola Larghi, Jens Geginat, Pier Luigi Meroni
OBJECTIVES: B cells play an important role in the initiation and progression of systemic lupus erythematosus (SLE). Accordingly, B cell-targeted therapy has been suggested as a new rational approach for treating lupus. Belimumab, a human monoclonal antibody directed against B lymphocyte stimulator (BLyS), was reported as the first biological treatment effective in reducing mild-to-moderate SLE disease activity by using different scoring systems and endpoints. Conversely clinical trials with rituximab, a chimeric monoclonal antibody directed against the CD20 expressed by B cells, have failed to achieve primary endpoints in spite of a number of reports showing its beneficial effects...
February 27, 2018: Clinical and Experimental Rheumatology
Glenwood D Goss, Everett E Vokes, Michael S Gordon, Leena Gandhi, Kyriakos P Papadopoulos, Drew W Rasco, JuDee S Fischer, Katharine L Chu, William W Ames, Rajendar K Mittapalli, Ho-Jin Lee, Jiewei Zeng, Lisa A Roberts-Rapp, Lise I Loberg, Peter J Ansell, Edward B Reilly, Christopher J Ocampo, Kyle D Holen, Anthony W Tolcher
BACKGROUND: Epidermal growth factor receptor (EGFR) alterations are associated with multiple cancers. Current EGFR-directed therapies have led to increased efficacy but are associated with specific side effects. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor-specific. METHODS: This phase 1/2 study evaluated the safety, pharmacokinetics, and efficacy of depatux-m in patients who had advanced solid tumors with known wild-type EGFR overexpression, amplification, or mutated EGFR variant III...
March 13, 2018: Cancer
Yoshiya Tanaka, Tsutomu Takeuchi, Masayoshi Harigai, Hisashi Yamanaka, Toshikazu Nakano, Koshiro Akagi, Yoshifumi Ukyo, Benjamin Hsu
Objective To evaluate the efficacy and safety of sirukumab, a human anti-interleukin 6 monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy. Methods This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed...
March 13, 2018: Modern Rheumatology
Toni K Choueiri, James Larkin, Mototsugu Oya, Fiona Thistlethwaite, Marcella Martignoni, Paul Nathan, Thomas Powles, David McDermott, Paul B Robbins, David D Chism, Daniel Cho, Michael B Atkins, Michael S Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Camilla Fowst, Alessandra di Pietro, Brian I Rini
BACKGROUND: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma...
March 9, 2018: Lancet Oncology
Sophie E Berends, Anne S Strik, Juliet C Van Selm, Mark Löwenberg, Cyriel Y Ponsioen, Geert R DʼHaens, Ron A Mathôt
BACKGROUND: A significant proportion of patients with Crohn's disease (CD) require dose escalation or fail adalimumab (ADL) therapy over time. ADL, a monoclonal antibody directed against tumor necrosis factor, is approved for treatment of CD. Understanding pharmacokinetics (PK) of ADL is essential to optimize individual dosing in daily practice. The aim of this study was to evaluate PK of ADL in patients with CD and to identify factors that influence PK of ADL. METHODS: In a retrospective cohort study, the authors reviewed the charts of 96 patients with CD receiving ADL induction and maintenance treatment...
April 2018: Therapeutic Drug Monitoring
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
Yongchang Lai, Zhijian Zhao, Tao Zeng, Xiongfa Liang, Dong Chen, Xiaolu Duan, Guohua Zeng, Wenqi Wu
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel-Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy...
2018: Cancer Cell International
Carminia Maria Della Corte, Vincenza Ciaramella, Claudia Cardone, Silvia La Monica, Roberta Alfieri, Pier Giorgio Petronini, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Maria Domenica Castellone, Teresa Troiani, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo
HYPOTHESIS: Osimertinib showed great clinical efficacy for activated-EGFR-NSCLC patients treatment. The aim of this work was to test the efficacy of a complete EGFR-inhibition by osimertinib plus the monoclonal antibody, cetuximab, or the MEK1/2-inhibitor, selumetinib, in EGFR-mutated-NSCLC in vivo models. METHODS: We evaluated combinations of osimertinib plus selumetinib/cetuximab in HCC827 (E746-A759del/T790M-), H1975 (L858R/T790M+) and PC9-T790M (E746-A759del /T790M+) xenografts, in second-line after the developing of resistance to osimertinib and in first-line, and we explored mechanisms of resistance to these treatments...
March 8, 2018: Journal of Thoracic Oncology
Virginia Devonshire, Richard Phillips, Hilary Wass, Gerald Da Roza, Peter Senior
Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared with subcutaneous interferon-beta-1a, alemtuzumab significantly reduced clinical disease activity and the rate of brain volume loss, and improved disability outcomes in patients with active RRMS who were either treatment naive (CARE-MS I study) or who had an inadequate response (≥ 1 relapse after ≥ 6 months of treatment) to prior therapy (CARE-MS II study)...
March 10, 2018: Journal of Neurology
Miriam Steinberg, Joseph P Gaut, Stanley Paul Hmiel, Aadil Kakajiwala
Monoclonal gammopathies are a rare diagnosis in pediatric patients. A 19-year-old female patient with past medical history of hypogammaglobulinemia and natural killer cell deficiency and stage III follicular lymphoma, in remission, presented with a right-sided pneumonia, noted to have acute kidney injury and proteinuria. Complement C3 and C4 levels were normal. Anti-double-stranded DNA antibodies, antinuclear antibodies, anti-extractable nuclear antigen antibodies, and antineutrophil cytoplasmic antibodies were negative...
March 9, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Meghdad Abdollahpour-Alitappeh, Seyed Masoud Hashemi Karouei, Majid Lotfinia, Amir Amanzadeh, Mahdi Habibi-Anbouhi
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE)...
March 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Lionel Kankeu Fonkoua, Nelson S Yee
Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively...
March 9, 2018: Biomedicines
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