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monoclonal antibodies in therapy

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https://www.readbyqxmd.com/read/28346048/mabdelivery-administration-routes-for-antibody-therapy-third-labex-mabimprove-industrial-workshop-july-2-2015-tours-france
#1
Elsa Bodier-Montagutelli, Renaud Respaud, Hervé Watier, Audrey Guillon-Munos
The annual "LabEx MAbImprove Industrial Workshops" are primarily intended to provide a comprehensive view about topics of interest for the pharmaceutical industry to scientists involved in research on therapeutic antibodies. The third workshop in this series, held July 2, 2015 in Tours, was dedicated to the optimization of delivery, namely all processes leading monoclonal antibodies to reach their target site. The commonly used intravenous (IV) route, although advantageous in terms of pharmacokinetics and pharmacodynamics, presents some disadvantages in terms of patients' convenience, therapeutic target access or treatment cost...
February 28, 2017: MAbs
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#2
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344809/basal-cell-carcinoma-pd-l1-pd-1-checkpoint-expression-and-tumor-regression-after-pd-1-blockade
#3
Evan J Lipson, Mohammed T Lilo, Aleksandra Ogurtsova, Jessica Esandrio, Haiying Xu, Patricia Brothers, Megan Schollenberger, William H Sharfman, Janis M Taube
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344579/reslizumab-and-eosinophilic-asthma-one-step-closer-to-precision-medicine
#4
REVIEW
Gilda Varricchi, Gianenrico Senna, Stefania Loffredo, Diego Bagnasco, Matteo Ferrando, Giorgio Walter Canonica
Human eosinophils represent approximately 1% of peripheral blood leukocytes. However, these cells have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophilic inflammation is present in a significant proportion of patients with severe asthma. Asthma is a chronic inflammatory disorder that affects more than 315 million people worldwide, with 10% having severe uncontrolled disease. Although the majority of patients can be efficiently treated, severe asthmatics continue to be uncontrolled and are at risk of exacerbations and even death...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28343601/effects-of-rg7652-a-monoclonal-antibody-against-pcsk9-on-ldl-c-ldl-c-subfractions-and-inflammatory-biomarkers-in-patients-at-high-risk-of-or-with-established-coronary-heart-disease-from-the-phase-2-equator-study
#5
Amos Baruch, Sofia Mosesova, John D Davis, Nageshwar Budha, Alexandr Vilimovskij, Robert Kahn, Kun Peng, Kyra J Cowan, Laura Pascasio Harris, Thomas Gelzleichter, Josh Lehrer, John C Davis, Whittemore G Tingley
RG7652 (MPSK3169A), a fully human immunoglobulin G1 (IgG1) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), blocks the interaction between PCSK9 and low-density lipoprotein (LDL) receptor. EQUATOR (ClinicalTrials.govNCT01609140), a randomized, double-blind, and dose-ranging phase 2 study, evaluated RG7652 in patients (1) at high risk for or (2) with coronary heart disease (CHD). The primary end point was change in LDL cholesterol (LDL-C) from baseline to day 169. Patients (n = 248; median age, 64 years; 57% men; 52% with established CHD; 82% on statins) with baseline LDL-C levels of 90 to 250 mg/dl (mean, 126 mg/dl) continuing on standard-of-care therapy were randomized to receive 1 of 5 RG7652 doses or placebo, subcutaneously every 4, 8, or 12 weeks for 24 weeks...
March 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28343171/circulating-free-light-chain-measurement-in-the-diagnosis-prognostic-assessment-and-evaluation-of-response-of-al-amyloidosis-comparison-of-freelite-and-n-latex-flc-assays
#6
Giovanni Palladini, Arnaud Jaccard, Paolo Milani, David Lavergne, Andrea Foli, Sebastien Bender, Francesca Lavatelli, Tiziana Bosoni, Veronica Valentini, Laura Pirolini, Giovanni Ferraro, Marco Basset, Francesca Russo, Mario Nuvolone, Riccardo Albertini, Michel Cogne, Giampaolo Merlini
BACKGROUND: The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe...
March 27, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28341874/the-multi-faceted-potential-of-cd38-antibody-targeting-in-multiple-myeloma
#7
Rory M Shallis, Christopher M Terry, Seah H Lim
CD38, an adenine dinucleotide phosphate (ADP) ribose cyclase and a cyclic ADP ribose hydrolase, is widely expressed on the surface of multiple myeloma (MM) cells. It is known to play a pivotal role in the downstream pathways that mediate MM cell growth, signal transduction, and adhesion. The clinical use of CD38 monoclonal antibodies (MoAbs), such as daratumumab, either as monotherapy or in combination with other anti-MM agents, has produced impressive results in patients who have failed standard MM therapy...
March 24, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#8
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#9
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#10
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
March 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28335637/reversing-the-anticoagulation-effects-of-dabigatran
#11
William E Dager, Linda Banares
The standard of care for oral anticoagulation therapy has primarily been warfarin, which is limited by its indirect mechanism-of-action, variable kinetics, tolerability, and routine monitoring concerns. The direct-acting oral anticoagulants (DOACs) have predictable pharmacokinetics and pharmacodynamics, and improved safety and efficacy compared to warfarin for the prevention of stroke in patients with nonvalvular atrial fibrillation and prevention or management of venous thromboembolism. Consequential bleeding is a concern with all anticoagulants...
March 24, 2017: Hospital Practice (Minneapolis)
https://www.readbyqxmd.com/read/28333127/selective-intracellular-vaporisation-of-antibody-conjugated-phase-change-nano-droplets-in-vitro
#12
A Ishijima, K Minamihata, S Yamaguchi, S Yamahira, R Ichikawa, E Kobayashi, M Iijima, Y Shibasaki, T Azuma, T Nagamune, I Sakuma
While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#13
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#14
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#15
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#16
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28329405/a-review-of-guselkumab-an-il-23-inhibitor-for-moderate-to-severe-plaque-psoriasis
#17
Z Nawas, M Hatch, E Ramos, M Liu, Y Tong, A Peranteau, S Tyring
Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28329114/pcsk9-monoclonal-antibodies-reverse-the-pro-inflammatory-profile-of-monocytes-in-familial-hypercholesterolaemia
#18
Sophie J Bernelot Moens, Annette E Neele, Jeffrey Kroon, Fleur M van der Valk, Jan Van den Bossche, Marten A Hoeksema, Renate M Hoogeveen, Johan G Schnitzler, Marie T Baccara-Dinet, Garen Manvelian, Menno P J de Winther, Erik S G Stroes
Aims: Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated low-density lipoprotein cholesterol (LDL-C) levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) which selectively reduce LDL-C, we studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328624/long-term-maintenance-of-clinical-endoscopic-and-radiographic-response-to-ustekinumab-in-moderate-to-severe-crohn-s-disease-real-world-experience-from-a-multicenter-cohort-study
#19
Christopher Ma, Richard N Fedorak, Gilaad G Kaplan, Levinus A Dieleman, Shane M Devlin, Nathan Stern, Karen I Kroeker, Cynthia H Seow, Yvette Leung, Kerri L Novak, Brendan P Halloran, Vivian W Huang, Karen Wong, Philip K Blustein, Subrata Ghosh, Remo Panaccione
BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohn's disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. METHODS: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016...
March 21, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28326566/systematic-review-with-meta-analysis-comparative-efficacy-of-biologics-for-induction-and-maintenance-of-mucosal-healing-in-crohn-s-disease-and-ulcerative-colitis-controlled-trials
#20
REVIEW
A Cholapranee, G S Hazlewood, G G Kaplan, L Peyrin-Biroulet, A N Ananthakrishnan
BACKGROUND: Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. AIM: To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC...
March 22, 2017: Alimentary Pharmacology & Therapeutics
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