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monoclonal antibodies in therapy

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https://www.readbyqxmd.com/read/28636484/bezlotoxumab-anti-toxin-b-monoclonal-antibody-to-prevent-recurrence-of-clostridium-difficile-infection
#1
Javier A Villafuerte Gálvez, Ciarán P Kelly
Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management...
June 21, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28636184/pharmacokinetics-pharmacodynamics-of-bococizumab-a-monoclonal-antibody-to-pcsk9-after-single-subcutaneous-injection-at-3-sites-nct-02043301
#2
Ellen Q Wang, Anna Plotka, Joanne Salageanu, Catherine Sattler, Carla Yunis
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28635659/divergent-how-ige-axis-contributes-to-the-continuum-of-allergic-asthma-and-anti-ige-therapies
#3
REVIEW
Óscar Palomares, Silvia Sánchez-Ramón, Ignacio Dávila, Luis Prieto, Luis Pérez de Llano, Marta Lleonart, Christian Domingo, Antonio Nieto
Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#4
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#5
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633038/hematopoietic-cell-transplantation-for-diffuse-large-b-cell-and-follicular-lymphoma-current-controversies-and-advances
#6
REVIEW
Narendranath Epperla, Mehdi Hamadani
Non-Hodgkin's lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with diverse biologic, histologic, and clinical features. With a better understanding of the molecular pathogenesis, recently there have been major advances in the treatment of NHLs including addition of novel monoclonal antibodies, targeted therapies, and immune activators to the therapy armamentarium. Despite these remarkable developments, autologous hematopoietic cell transplantation (auto-HCT) remains not only a standard-of-care curative option for aggressive NHL but also an important therapeutic option for indolent NHL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28632865/effect-of-first-line-chemotherapy-combined-with-cetuximab-or-bevacizumab-on-overall-survival-in-patients-with-kras-wild-type-advanced-or-metastatic-colorectal-cancer-a-randomized-clinical-trial
#7
Alan P Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Briant Fruth, Jeffrey A Meyerhardt, Deborah Schrag, Claire Greene, Bert H O'Neil, James Norman Atkins, Scott Berry, Blase N Polite, Eileen M O'Reilly, Richard M Goldberg, Howard S Hochster, Richard L Schilsky, Monica M Bertagnolli, Anthony B El-Khoueiry, Peter Watson, Al B Benson, Daniel L Mulkerin, Robert J Mayer, Charles Blanke
Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28631382/a-phase-ii-trial-evaluating-the-feasibility-of-adding-bevacizumab-to-standard-osteosarcoma-therapy
#8
Fariba Navid, Victor M Santana, Michael Neel, M Beth McCarville, Barry L Shulkin, Jianrong Wu, Catherine A Billups, Shenghua Mao, Vinay M Daryani, Clinton F Stewart, Michelle Kunkel, Wendene Smith, Deborah Ward, Alberto S Pappo, Armita Bahrami, David M Loeb, Jennifer Reikes Willert, Bhaskar N Rao, Najat C Daw
Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received 2 courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy...
June 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#9
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28629323/fetal-death-in-utero-and-miscarriage-in-a-patient-with-crohn-s-disease-under-therapy-with-ustekinumab-case-report-and-review-of-the-literature
#10
C Venturin, S Nancey, P Danion, M Uzzan, M Chauvenet, C Bergoin, X Roblin, B Flourié, G Boschetti
BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#11
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#12
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28626406/late-onset-inflammatory-bowel-disease-like-syndrome-after-ipilimumab-therapy-a-case-report
#13
Reem Akel, Bilal Anouti, Arafat Tfayli
BACKGROUND: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28626166/efficacy-of-denosumab-for-osteoporosis-in-three-female-patients-with-osteogenesis-imperfecta
#14
Masashi Uehara, Yukio Nakamura, Jun Takahashi, Mikio Kamimura, Shota Ikegami, Takako Suzuki, Shigeharu Uchiyama, Tomomi Yamaguchi, Tomoki Kosho, Hiroyuki Kato
Osteogenesis imperfecta (OI) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of OI to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28624108/modification-of-immunosuppressive-therapy-as-risk-factor-for-complications-after-liver-transplantation
#15
REVIEW
Paolo De Simone, Paola Carrai, Laura Coletti, Davide Ghinolfi, Stefania Petruccelli, Franco Filipponi
Management of complications post-liver transplantation (LT) includes immunosuppressive manipulations with the aim to reduce the overall burden of immunologic suppression and compensate for renal, cardiovascular, metabolic toxicities, and for the increased oncologic risk. Two approaches can be implemented to reduce immunosuppression-related adverse events: upfront schedules tailored to the pretransplant individual patient's risk profile versus downstream modifications in the event of immunosuppression-related complications...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28623954/efficacy-and-safety-of-alirocumab-in-patients-with-hypercholesterolemia-not-adequately-controlled-with-non-statin-lipid-lowering-therapy-or-the-lowest-strength-of-statin-odyssey-nippon-study-design-and-rationale
#16
Tamio Teramoto, Akira Kondo, Arihiro Kiyosue, Mariko Harada-Shiba, Yasushi Ishigaki, Kimimasa Tobita, Yumiko Kawabata, Asuka Ozaki, Marie T Baccara-Dinet, Masataka Sata
BACKGROUND: Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). METHODS: The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone)...
June 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28623267/a-new-paradigm-for-antiangiogenic-therapy-through-controlled-release-of-bevacizumab-from-plga-nanoparticles
#17
Flávia Sousa, Andrea Cruz, Pedro Fonte, Inês Mendes Pinto, Maria Teresa Neves-Petersen, Bruno Sarmento
Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623233/structural-and-functional-analyses-of-pyroglutamate-amyloid-%C3%AE-specific-antibodies-as-a-basis-for-alzheimer-immunotherapy
#18
Anke Piechotta, Christoph Parthier, Martin Kleinschmidt, Kathrin Gnoth, Thierry Pillot, Inge Lues, Hans-Ulrich Demuth, Stephan Schilling, Jens-Ulrich Rahfeld, Milton T Stubbs
Alzheimers disease is associated with deposition of the amyloidogenic peptide Aβ in the brain. Passive immunization using Aβ-specific antibodies has been demonstrated to reduce amyloid deposition both in vitro and in vivo. As N terminally truncated pyroglutamate (pE)-modified Aβ species (AβpE3) exhibit enhanced aggregation potential and propensity to form toxic oligomers, they represent particularly attractive targets for antibody therapy. Here we present three separate monoclonal antibodies that specifically recognize AβpE3 with affinities of 1-10 nM and inhibit AβpE3 fibril formation in vitro...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28619061/rituximab-versus-cyclophosphamide-for-the-treatment-of-connective-tissue-disease-associated-interstitial-lung-disease-recital-study-protocol-for-a-randomised-controlled-trial
#19
Peter Saunders, Vicky Tsipouri, Gregory J Keir, Deborah Ashby, Marcus D Flather, Helen Parfrey, Daphne Babalis, Elisabetta A Renzoni, Christopher P Denton, Athol U Wells, Toby M Maher
BACKGROUND: Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little...
June 15, 2017: Trials
https://www.readbyqxmd.com/read/28618994/role-of-anti-pcsk9-antibodies-in-the-treatment-of-patients-with-statin-intolerance
#20
Julia Schreml, Ioanna Gouni-Berthold
Statin intolerance is usually defined as the inability of a patient to tolerate statin-treatment due to muscle-related complaints. While randomised trials show that these complaints occure with similar frequency in patients receiving placebo, namely in up to ~5% of the subjects, data from registries as well as clinical experience indicate a much higher frequency of up to ~30%. The lack of standard definition or of a diagnostic marker of statin intolerance confounds the problem. The diagnosis remains subjective based on the symptoms the patient reports...
June 16, 2017: Current Medicinal Chemistry
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