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Monoclonal protein

Beate Hintersteiner, Nico Lingg, Evelyne Janzek, Oliver Mutschlechner, Hans Loibner, Alois Jungbauer
It has previously been shown for individual antibodies, that the microheterogenity pattern can have a significant impact on various key characteristics of the product. The aim of this study to get a more generalized understanding of the importance of microheterogeneity. For that purpose, the charge variant pattern of various different commercially available therapeutic mAb products was compared using Cation-Exchange Chromatography with linear pH gradient antigen affinity, Fc-receptor affinity, antibody dependent cellular cytotoxicity (ADCC) and conformational stability...
October 18, 2016: Biotechnology Journal
A L J J Bronckers, R Jalali, J Lytton
Exposure of forming enamel to fluoride results into formation of hypomineralized enamel. We tested whether enamel hypomineralization was caused by lower expression of the NCKX4/SLC24A4 Ca(2+)-transporter by ameloblasts. Three commercial antibodies against NCKX4 were tested on enamel organs of wild-type and Nckx4-null mice, one of which (a mouse monoclonal) was specific. This antibody gave a prominent staining of the apical plasma membranes of maturation ameloblasts, starting at early maturation. The layer of immuno-positive ameloblasts contained narrow gaps without immunostaining or with reduced staining...
October 17, 2016: Calcified Tissue International
Sashka Krumova, Svetla Todinova, Deyan Mavrov, Pencho Marinov, Vassia Atanassova, Krassimir Atanassov, Stefka G Taneva
BACKGROUND: Biological microcalorimetry has entered into a phase where its potential for disease diagnostics is readily recognized. A wide variety of oncological and immunological disorders have been characterized by differential scanning calorimetry (DSC) and characteristic thermodynamic profiles were reported. Now the challenge before DSC is not the experimental data collection but the development of analysis protocols for reliable data stratification/classification and discrimination of disease specific features (calorimetric markers)...
October 15, 2016: Biochimica et Biophysica Acta
Antonino Carbone, Annunziata Gloghini, Arnaldo Caruso, Paolo De Paoli, Riccardo Dolcetti
The pathogenesis of classical Hodgkin lymphoma (cHL) is still enigmatic, largely because its tumor cells, the so-called Hodgkin and Reed-Stenberg (HRS) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. On the other hand, the broadly investigated cHL-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. Based on current knowledge, it appears that the cross talk between the tumour cells and the reactive infiltrate of the microenvironment is complex and that multiple mechanisms occur, making cHL a very heterogeneous disease...
October 17, 2016: International Journal of Cancer. Journal International du Cancer
Patrizio Caturegli, Giulia Di Dalmazi, Martina Lombardi, Federica Grosso, H Benjamin Larman, Tatianna Larman, Giacomo Taverna, Mirco Cosottini, Isabella Lupi
Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathological examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathological evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function...
October 14, 2016: American Journal of Pathology
Hitomi Hoshino, Makoto Ohta, Makoto Ito, Kenji Uchimura, Yasuhiro Sakai, Takeshi Uehara, Shulin Low, Mana Fukushima, Motohiro Kobayashi
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver neoplasm, followed by hepatocellular carcinoma. ICC can be further subclassified as (i) perihilar and (ii) peripheral types, the latter histologically resembling small-sized intrahepatic bile ducts, such as interlobular bile ducts, cholangioles/ductules and the canals of Hering. Cholangiolocellular carcinoma (CoCC), now classified by the World Health Organization as a subtype of combined hepatocellular-cholangiocarcinoma, is currently regarded as a subtype of peripheral-type ICC...
October 17, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Sagadevan Kalaiselvan, Sathish Sankar, Mageshbabu Ramamurthy, Asit Ranjan Ghosh, Balaji Nandagopal, Gopalan Sridharan
Hantavirus infections are now recognized to be a global problem. The hantaviruses include several genotypic variants of the virus with different distributions in varying geographical regions. The virus genotypes seem to segregate in association with certain manifestations specific for each syndrome. They primarily include HFRS, HCPS, febrile illness with or without mild involvement of renal diseases. In the course of our study on hantavirus etiology of febrile illnesses, we recovered a hantavirus strain identified by nPCR...
October 17, 2016: Journal of Cellular Biochemistry
Anita Chopra, Sushant Soni, Haraprasad Pati, Dev Kumar, Rahul Diwedi, Deepak Verma, Garima Vishwakama, Sameer Bakhshi, Suman Kumar, Ajay Gogia, Rajive Kumar
BACKGROUND & OBJECTIVES: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple substitute for the standard screening molecular method...
June 2016: Indian Journal of Medical Research
Surbhi Goyal, Kiran Mishra, Urvee Sarkar, Satendra Sharma, Anita Kumari
BACKGROUND & OBJECTIVES: Renal tumours constitute about 7 per cent of all neoplasms in children. It is important to differentiate Wilms' tumour (commonest tumour) from non-Wilms' tumours. The aim of this study was to evaluate the immunoexpression and diagnostic role of Wilms' tumour-1 protein (WT1) in paediatric renal tumours. METHODS: A total of 53 cases of renal tumours in children (below 18 yr) who underwent total nephrectomy were included in this retrospective study...
May 2016: Indian Journal of Medical Research
Marc D Cohen, Edward Keystone
Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors...
December 2015: Rheumatol Ther
Jun Gong, May Cho, Marwan Fakih
The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway...
October 2016: Journal of Gastrointestinal Oncology
Yosuke Kameda, Motoki Hanayama, Atsushi Kishimoto, Masahiko Kume, Kazuo Yamamoto, Naoki Matsumoto
Dendritic cell inhibitory receptor 4 (DCIR4, Clec4a1) is a lectin receptor and a member of mouse dendritic cell immunoreceptor family. Due to the lack of antibodies against DCIR4, expression of DCIR4 protein remains unknown. In this study, we established a specific monoclonal antibody against DCIR4 and investigated the expression of DCIR4 among immune cells. We found that DCIR4 was expressed on non-granulocytic subsets of CD11b(+) cells in various immune organs including bone marrow, peripheral blood, spleen, skin-associated lymph nodes and mesenteric lymph nodes...
October 13, 2016: Biochemical and Biophysical Research Communications
Cecilia Rossetti, Maren C S Levernæs, Léon Reubsaet, Trine G Halvorsen
Mass spectrometric assays are now of great relevance for trace compound analysis in complex matrices such as serum and plasma samples. Especially in the quantification of low abundant protein-biomarkers, the choice of the sample preparation is crucial. In the present paper immunocapture and Molecular Imprinted Polymers (MIPs) have been applied in the determination of pro-gastrin-releasing peptide, a Small Cell Lung Cancer marker. These affinity-based techniques were compared in terms of matrix effect, limits of detection, repeatability and extraction specificity...
October 1, 2016: Journal of Chromatography. A
Buka Samten, Stewart Fannin, Krishna Sarva, Na Yi, Murty Madiraju, Malini Rajagopalan
Mycobacterium tuberculosis secretes a number of proteins into the extracellular milieu during growth. Several of these proteins have been associated with modulation of the host immune response. Antigen 84, or Wag31, is one such protein that is conserved among all mycobacterial species and is recognized by the sera from tuberculosis and leprosy patients. Here, we examined the effect of Wag31 on the ability of activated human T cells to produce cytokines such as IL-10, IL-17 and IFN-γ in response to combined anti-CD3 and anti-CD28 stimulation...
September 28, 2016: Tuberculosis
Rima Matsuyama, Noriko Yamano, Namiko Kawamura, Takeshi Omasa
The establishment process of high-producing Chinese hamster ovary (CHO) cells for therapeutic protein production is usually laborious and time consuming because of the low probability of obtaining stable, high-producing clones over a long term. Thus, development of an efficient approach is required to establish stable, high-producing cells. This study presents a novel method that can efficiently establish sustainably high-producing cell lines by acceleration of transgene amplification and suppression of transgene silencing...
October 12, 2016: Journal of Bioscience and Bioengineering
Hongjiu Yu, Yonggui Ge, Lianying Guo, Lin Huang
Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise...
October 11, 2016: Oncotarget
Saloumeh Kadkhodayan Fischer, Melissa Cheu, Kun Peng, John Lowe, James Araujo, Elaine Murray, Dana McClintock, John Matthews, Patricia Siguenza, An Song
Host cell proteins are manufacturing process-related impurities that may co-purify with the product despite extensive efforts to optimize the purification process. The risks associated with these impurities can vary and may be patient and/or therapeutic dependent. Therefore, it is critical to monitor and control the levels of these impurities in products and their potential impact on safety and efficacy. Lebrikizumab is a humanized immunoglobulin G4 monoclonal antibody (mAb) that binds specifically to soluble interleukin 13...
October 13, 2016: AAPS Journal
Ting-Ting Han, Shuang Zheng, Zeng-Ai Chen, Wei Liu, Yao-Min Hu
POEMS syndrome is a rare multi-systemic disease characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. Arterial thrombosis is a distinctively unusual feature in patients with POEMS syndrome. We report a 33-year-old man with intermittent amaurosis of left eye and skin changes as the onset manifestations, who was finally confirmed as having POEMS syndrome. Most notably, this was a young man without high risk factors of arterial thrombosis and no monoclonal protein was detected until the repeated measurement later...
October 11, 2016: Oncotarget
Roger A Levy, Renato Guzman, Gilberto Castañeda-Hernández, Manuel Martinez-Vazquez, Guilherme Damian, Carlos Cara
Biologics are increasingly being used to modify the course of immune-mediated inflammatory diseases. Some main agents are monoclonal antibodies and a fusion-protein that target TNF. This group includes adalimumab, infliximab, certolizumab pegol, golimumab and etanercept. Although the efficacy of anti-TNFs is supported by numerous randomized clinical trials, their pharmacokinetics depend on many factors, in particular immunogenicity, which can cause marked and rapid clearance and a consequent decrease in efficacy...
October 14, 2016: Immunotherapy
Roshan Ashoor, Dong Lee, Alvan Cheng, Bart Jessen, Wenhu Huang
PURPOSE: PF-06653157 is a bifunctional antagonist monoclonal antibody (mAb) that targets human VEGF-A ligand and PDGF-Rβ. With the advent of PF-06653157 as an angiogenesis inhibitor and potential treatment for angiogenesis deregulation diseases, a relevant toxicology species is needed for toxicity and efficacy studies. Investigative studies were conducted to validate the mAb dual antagonist properties in a human system and determine its cross-reactive pharmacology in nonhuman cells. METHODS: Sequence alignment was used to determine percent sequence identity of VEGF and PDGF receptors and ligands; qualitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the presence of PDGF-Rβ on cells of interest...
October 13, 2016: Journal of Ocular Pharmacology and Therapeutics
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