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monoclonal treatment

Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
Bella H V Nguyen, James Kuo, Anadian Budiman, Hayden Christie, Sayed Ali
Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients...
October 21, 2016: Melanoma Research
Mary Jc Hendrix, Irawati Kandela, Andrew P Mazar, Elisabeth A Seftor, Richard Eb Seftor, Naira V Margaryan, Luigi Strizzi, George F Murphy, Georgina V Long, Richard A Scolyer
Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of <6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
A Dokala, S S Thakur
The epidermal growth factor receptor (EGFR) is a transmembrane receptor with tyrosine kinase activity involved in regulation of cellular multiplication, survival, differentiation and metastasis. Our knowledge about function and complex management of these receptors has driving the development of specific and targeted treatment modalities for human cancers in the last 20 years. EGFR is the first receptor target against which monoclonal antibodies (mAb) have been evolved for cancer treatment. Here we review the biology of ErbB receptors, including their architecture, signaling, regulation and therapeutic strategies and the mechanisms of resistances offered by the receptors against small-molecule tyrosine kinases and resistance overcome implications of mAbs...
October 24, 2016: Oncogene
John Nixon, Paul Newbold, Tomas Mustelin, Gary P Anderson, Roland Kolbeck
Eosinophils have been linked with asthma for more than a century, but their role has been unclear. This review discusses the roles of eosinophils in asthma and chronic obstructive pulmonary disease (COPD) and describes therapeutic antibodies that affect eosinophilia. The aims of pharmacologic treatments for pulmonary conditions are to reduce symptoms, slow decline or improve lung function, and reduce the frequency and severity of exacerbations. Inhaled corticosteroids (ICS) are important in managing symptoms and exacerbations in asthma and COPD...
October 20, 2016: Pharmacology & Therapeutics
Frank Bridoux, Vincent Javaugue, Sébastien Bender, Fannie Leroy, Pierre Aucouturier, Céline Debiais-Delpech, Jean-Michel Goujon, Nathalie Quellard, Amélie Bonaud, Marie Clavel, Patrick Trouillas, Florent Di Meo, Jean-Marc Gombert, Jean-Paul Fermand, Arnaud Jaccard, Michel Cogné, Guy Touchard, Christophe Sirac
Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by tissue deposition of a truncated monoclonal immunoglobulin heavy chain lacking the first constant domain. Pathophysiological mechanisms are unclear and management remains to be defined. Here we retrospectively studied 15 patients with biopsy-proven HCDD of whom 14 presented with stage 3 or higher chronic kidney disease, with nephrotic syndrome in 9. Renal lesions were characterized by nodular glomerulosclerosis, with linear peritubular and glomerular deposits of γ-heavy chain in 12 patients or α-heavy chain in 3 patients, without concurrent light chain staining...
October 20, 2016: Kidney International
Mark R Gilbert, Stephanie L Pugh, Ken Aldape, A Gregory Sorensen, Tom Mikkelsen, Marta Penas-Prado, Felix Bokstein, Young Kwok, R Jeffrey Lee, Minesh Mehta
Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age ≥18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m(2) every 2 weeks or temozolomide (TMZ) 75-100 mg/m(2) day 1-21 of 28 day cycle...
October 21, 2016: Journal of Neuro-oncology
Soraya Sajadimajd, Razieh Yazdanparast
Trastuzumab (Herceptin) monoclonal antibody directed against HER2 receptor has been administered as a treatment for metastatic HER2 positive breast cancer. The problematic issue in treatment of HER2 positive breast cancer cells is commonly the induction of resistance to trastuzumab which might be due to modulation of some vital signaling elements such as Notch1 and Pin1. In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
Danielle L Brunjes, Adam Castano, Autumn Clemons, Jonah Rubin, Mathew S Maurer
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques...
October 18, 2016: Journal of Cardiac Failure
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Valentina Talarico, Monica Aloe, Alice Monzani, Roberto Miniero, Gianni Bona
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption...
December 2016: Minerva Pediatrica
Y-M Chiu, C-H Tang, S-T Hung, Y-W Yang, C-H Fang, H-Y Lin
OBJECTIVES: Few studies on tumour necrosis factor (TNF) inhibitor-associated tuberculosis (TB) and hepatic events have been performed in regions where these risks are elevated. This study aimed to provide a direct comparison between adalimumab and etanercept in a high-risk population and to address the implications for physicians working with patients in such an environment. METHOD: Data collected from the National Health Insurance Research Database (NHIRD) in Taiwan between 2007 and 2011 were analysed retrospectively for incidences of eight adverse events associated with TNF-α inhibitors...
October 21, 2016: Scandinavian Journal of Rheumatology
Divya Samineni, Sandhya Girish, Chunze Li
Suboptimal treatment for monoclonal antibodies (mAbs) directed against endogenous circulating soluble targets and the shed extracellular domains (ECD) of the membrane-bound targets is an important clinical concern due to the potential impact of mAbs on the in vivo efficacy and safety. Consequently, there are considerable challenges in the determination of an optimal dose and/or dosing regimen. Areas covered: This review outlines the impact of shed antigen targets from membrane-bound proteins and soluble targets on the PK and/or PD of therapeutic mAbs that have been approved in the last decade...
October 21, 2016: Expert Review of Clinical Pharmacology
Sarah Elizabeth Skerratt, Mark D Andrews, Sharan K Bagal, James Bilsland, David Brown, Peter J Bungay, Susan Cole, Karl R Gibson, Russell Jones, Inaki Morao, Angus Nedderman, Kiyoyuki Omoto, Colin Robinson, Thomas Ryckmans, Kimberly Skinner, Paul Anthony Stupple, Gareth Waldron
The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially "druggable" point of intervention...
October 21, 2016: Journal of Medicinal Chemistry
Athanasios Tragiannidis, Ioannis Kyriakidis, Ilse Zündorf, Andreas H Groll
Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid-refractory graft-vs-host disease and other immune-mediated conditions...
October 21, 2016: Mycoses
Ágnes Márk, Gergely Varga, Botond Timár, Csilla Kriston, Orsolya Szabó, Linda Deák, András Matolcsy, Gábor Barna
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells (PCs) in the bone marrow and other tissues. Although there are several new therapies, MM remains fatal. The interaction between MM cells and the bone marrow microenvironment promotes drug resistance and cancer cells survival. In our present work, we compared the antigen expression pattern of normal and pathological PCs and investigated the possible connections between various surface receptors, adhesion molecules, and recurrent genetic aberrations...
October 21, 2016: Hematological Oncology
Hiroaki Matsuno
BACKGROUND AND OBJECTIVES: Recently, the osteoporosis treatment has attracted attention, and several drugs have been developed. Among these, bisphosphonates (BPs), parathyroid hormone (PTH) and anti-receptor activator of nuclear factor kappa B ligand (RANKL) monoclonal (MAb) denosumab (DMAb) are the major osteoporosis agents. Several studies demonstrated that the effect of osteoporosis agents is evaluated by lumar or hip dual energy X-ray absorptiometry (DXA). However, private clinic commonly use the radial DXA...
October 20, 2016: Drugs in R&D
Yu-Min Shen
Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disorder caused by defective complement regulation resulting in thrombotic microangiopathy (TMA). Patients can present as children or adults. The syndrome consists of hemolytic anemia with schistocytosis, thrombocytopenia, significant renal damage, and/or other organ system dysfunction(s). Patients with aHUS may succumb to the complications of the disease with the very first manifestation; surviving patients often suffer from progressive organ dysfunction with significant morbidity and mortality despite plasma infusion or plasma exchange...
2016: Thrombosis Journal
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