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https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#1
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28498096/characterization-of-the-anti-bovine-podoplanin-monoclonal-antibody-pmab-44
#2
Shinji Yamada, Ryusuke Honma, Mika K Kaneko, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Michiaki Takagi, Satoru Konnai, Yukinari Kato
A type I transmembrane sialoglycoprotein podoplanin (PDPN) is expressed in several normal cells, including podocytes of the kidney, type I alveolar cells of the lung, and lymphatic endothelial cells. We recently produced an anti-bovine PDPN (bovPDPN) monoclonal antibody (mAb), PMab-44, by immunizing mice with recombinant proteins of bovPDPN. In this study, we determined the critical epitope of PMab-44 for the recognition of bovPDPN using many deletion mutants and point mutants of bovPDPN. Flow cytometric analyses revealed that the epitope of PMab-44 was Glu46-Thr50, which corresponds to platelet aggregation-stimulating (PLAG) domain-3...
May 12, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28472993/humanized-monoclonal-antibody-armanezumab-specific-to-n-terminus-of-pathological-tau-characterization-and-therapeutic-potency
#3
Michael G Agadjanyan, Karen Zagorski, Irina Petrushina, Hayk Davtyan, Konstantin Kazarian, Maxim Antonenko, Joy Davis, Charles Bon, Mathew Blurton-Jones, David H Cribbs, Anahit Ghochikyan
BACKGROUND: The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time, pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore, targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation, becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28464235/multi-criteria-manufacturability-indices-for-ranking-high-concentration-monoclonal-antibody-formulations
#4
Yang Yang, Ajoy Velayudhan, Nina F Thornhill, Suzanne S Farid
The need for high-concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high-concentration mAb formulation conditions in terms of their ease of manufacture...
May 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28447132/high-throughput-analysis-of-sub-visible-mab-aggregate-particles-using-automated-fluorescence-microscopy-imaging
#5
Albert Jesuran Paul, Fabian Bickel, Martina Röhm, Lisa Hospach, Bettina Halder, Nina Rettich, René Handrick, Eva Maria Herold, Hans Kiefer, Friedemann Hesse
Aggregation of therapeutic proteins is a major concern as aggregates lower the yield and can impact the efficacy of the drug as well as the patient's safety. It can occur in all production stages; thus, it is essential to perform a detailed analysis for protein aggregates. Several methods such as size exclusion high-performance liquid chromatography (SE-HPLC), light scattering, turbidity, light obscuration, and microscopy-based approaches are used to analyze aggregates. None of these methods allows determination of all types of higher molecular weight (HMW) species due to a limited size range...
April 27, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28430651/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#6
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420529/separation-of-antibody-monomer-dimer-mixtures-by-frontal-analysis
#7
Jason M Reck, Timothy M Pabst, Alan K Hunter, Giorgio Carta
The removal of aggregates, particularly soluble dimers, from monoclonal antibodies (mAbs) remains a persistent challenge in downstream processing. In this work, we have examined the separation of an antibody monomer from its dimer on the cation exchange resin Nuvia HR-S (Bio-Rad Laboratories) using frontal analysis. In this process, a mixture of monomer and dimer is continuously fed to the column under conditions where the mixture is favorably bound, resulting in two breakthrough fronts whose monomer and dimer compositions are determined by the multi-component equilibrium and kinetics of the system...
April 10, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28416674/inducing-protein-aggregation-by-extensional-flow
#8
John Dobson, Amit Kumar, Leon F Willis, Roman Tuma, Daniel R Higazi, Richard Turner, David C Lowe, Alison E Ashcroft, Sheena E Radford, Nikil Kapur, David J Brockwell
Relative to other extrinsic factors, the effects of hydrodynamic flow fields on protein stability and conformation remain poorly understood. Flow-induced protein remodeling and/or aggregation is observed both in Nature and during the large-scale industrial manufacture of proteins. Despite its ubiquity, the relationships between the type and magnitude of hydrodynamic flow, a protein's structure and stability, and the resultant aggregation propensity are unclear. Here, we assess the effects of a defined and quantified flow field dominated by extensional flow on the aggregation of BSA, β2-microglobulin (β2m), granulocyte colony stimulating factor (G-CSF), and three monoclonal antibodies (mAbs)...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28405525/obinutuzumab-mediated-high-affinity-ligation-of-fc%C3%AE-riiia-cd16-primes-nk-cells-for-ifn%C3%AE-production
#9
Cristina Capuano, Chiara Pighi, Rosa Molfetta, Rossella Paolini, Simone Battella, Gabriella Palmieri, Giuseppe Giannini, Francesca Belardinilli, Angela Santoni, Ricciarda Galandrini
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28393238/modulation-of-interactions-of-neuroblastoma-cell-lines-with-extracellular-matrix-proteins-affects-their-sensitivity-to-treatment-with-the-anti-gd2-ganglioside-antibody-14g2a
#10
Irena Horwacik, Hanna Rokita
Children diagnosed with high risk neuroblastoma have poor prognosis which stimulates efforts to broaden therapies of the neoplasm. GD2-ganglioside (GD2) marks neuroblastoma cells and is a target for monoclonal antibodies. We have recently shown that some neuroblastoma cell lines are sensitive to direct cytotoxicity of the anti-GD2 mouse monoclonal antibody 14G2a (mAb). For IMR-32 and LA-N-1 cell lines, treatment with the 14G2a mAb induced evident changes in appearance such as cell rounding, aggregation, loose contact with culture plastic, or detachment...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28379093/single-amino-acid-substitution-in-lc-cdr1-induces-russell-body-phenotype-that-attenuates-cellular-protein-synthesis-through-eif2%C3%AE-phosphorylation-and-thereby-downregulates-igg-secretion-despite-operational-secretory-pathway-traffic
#11
Haruki Hasegawa, Ann Hsu, Christine E Tinberg, Karen E Siegler, Aaron A Nazarian, Mei-Mei Tsai
Amino acid sequence differences in the variable region of immunoglobulin (Ig) cause wide variations in secretion outputs. To address how a primary sequence difference comes to modulate immunoglobulin (Ig) secretion, we investigated the biosynthetic process of two human IgG2κ monoclonal antibodies (mAbs) that differ only by one amino acid in the light chain complementarity-determining region 1 whilst showing ∼20-fold variance in secretion titer. Although poorly secreted, the lower-secreting mAb of the two was by no means defective in terms of its folding stability, antigen binding, and in vitro biologic activity...
April 5, 2017: MAbs
https://www.readbyqxmd.com/read/28365979/a-multidimensional-analytical-comparison-of-remicade-and-the-biosimilar-remsima
#12
Karthik Pisupati, Yuwei Tian, Solomon Okbazghi, Alexander Benet, Rose Ackermann, Michael Ford, Sergei Saveliev, Christopher M Hosfield, Marjeta Urh, Eric Carlson, Christopher Becker, Thomas J Tolbert, Steven P Schwendeman, Brandon T Ruotolo, Anna Schwendeman
In April 2016, the Food and Drug Administration approved the first biosimilar monoclonal antibody (mAb), Inflectra/Remsima (Celltrion), based off the original product Remicade (infliximab, Janssen). Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility, and quantitative peptide mapping. The levels of oxidation, deamidation, and mutation of individual amino acids were remarkably similar...
April 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28345870/ultrafast-separation-and-analysis-of-monoclonal-antibody-aggregates-using-membrane-chromatography
#13
Pedram Madadkar, Umatheny Umatheva, Geoff Hale, Yves Durocher, Raja Ghosh
We discuss a method for rapid and cost-effective analysis of monoclonal antibody (mAb) aggregates. Hydrophobic interaction membrane chromatography, which was previously shown to be highly suitable for such separation and analysis, was used in a recently developed format referred to as laterally fed membrane chromatography (or LFMC). A stack of rectangular polyvinylidene fluoride (or PVDF) membranes having 0.22 μm pores housed within a modified analytical-scale LFMC device was used for analyzing aggregate types and content in different monoclonal antibody samples...
April 6, 2017: Analytical Chemistry
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
#14
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...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28285160/ethanol-dispersed-and-antibody-conjugated-polymer-nanofibers-for-the-selective-capture-and-3-dimensional-culture-of-epcam-positive-cells
#15
Junghyo Yoon, Hee-Sook Yoon, Yoojin Shin, Sanghyun Kim, Youngjun Ju, Jungbae Kim, Seok Chung
Electrospun and ethanol-dispersed polystyrene-poly(styrene-co-maleic anhydride) (PS-PSMA) nanofibers (NFs) were used as a platform for the selective capture and three-dimensional culture of EpCAM-positive cells in cell culture medium and whole blood. The NFs were treated with streptavidin to facilitate bond formation between the amino groups of streptavidin and the maleic anhydride groups of the NFs. A biotinylated anti-EpCAM monoclonal antibody (mAb) was attached to the streptavidin-conjugated NFs via the selective binding of streptavidin and biotin...
March 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28281648/proteomic-analysis-of-host-cell-protein-dynamics-in-the-culture-supernatants-of-antibody-producing-cho-cells
#16
Jin Hyoung Park, Jong Hwa Jin, Myung Sin Lim, Hyun Joo An, Jong Won Kim, Gyun Min Lee
Chinese hamster ovary (CHO) cells are the most common cell line used for the production of therapeutic proteins including monoclonal antibodies (mAbs). Host cell proteins (HCPs), secreted and released from lysed cells, accumulate extracellularly during the cultures of recombinant CHO (rCHO) cells, potentially impairing product quality. In an effort to maintain good mAb quality during the cultures, HCPs accumulated extracellularly in batch and fed-batch cultures of a mAb-producing rCHO cell line were identified and quantified by nanoflow liquid chromatography-tandem mass spectrometry, followed by their gene ontology and functional analysis...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264026/melanoma-cells-undergo-aggressive-coalescence-in-a-3d-matrigel-model-that-is-repressed-by-anti-cd44
#17
Deborah Wessels, Daniel F Lusche, Edward Voss, Spencer Kuhl, Emma C Buchele, Michael R Klemme, Kanoe B Russell, Joseph Ambrose, Benjamin A Soll, Aaron Bossler, Mohammed Milhem, Charles Goldman, David R Soll
Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model...
2017: PloS One
https://www.readbyqxmd.com/read/28248007/antibody-purification-from-cho-cell-supernatant-using-new-multimodal-membranes
#18
Juan Wang, Jinxiang Zhou, Yogender K Gowtham, Sarah W Harcum, Scott M Husson
This contribution describes strategies to purify monoclonal antibodies from Chinese hamster ovary (CHO) cell culture supernatant using newly designed multimodal membranes (MMMs). The MMMs were used for the capture step purification of human IgG1 following a size-exclusion desalting column to remove chaotropic salts that interfere with IgG binding. The MMM column attained higher dynamic binding capacity than a Protein A resin column at an equivalent residence time of 1 min. The two step MMM chromatography process achieved high selectivity for capturing hIgG1 from the CHO cell culture supernatant, though the desalting step resulted in product dilution...
March 1, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28242491/identification-and-characterization-of-monoclonal-antibody-fragments-cleaved-at-the-complementarity-determining-region-using-orthogonal-analytical-methods
#19
Wenhua Li, Bin Yang, Dongmei Zhou, Jun Xu, Wenjia Li, Wen-Chen Suen
Sodium dodecyl sulfate capillary electrophoresis (CE-SDS) has been widely used to separate and quantify monoclonal antibody (mAb) fragments and impurities. Two fragments with different masses smaller than monomer were observed in the CE-SDS analysis of a recombinant IgG1 mAb treated at 40°C for 28days. Reversed phase liquid chromatography mass spectrometry (RP-LC-MS) and trypsin digestion peptide mapping followed by LC-MS/MS analysis were employed to conclusively demonstrate that these antibody fragments were the degradation products derived from a Ser-Ser peptide bond cleavage at the heavy chain complementarity determining region (CDR)...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28220238/application-of-calcium-phosphate-flocculation-in-high-density-cell-culture-fluid-with-high-product-titer-of-monoclonal-antibody
#20
Guoqiang Chen, Zhiguo Su, Feng Li, Hui Fang Liu
The calcium phosphate [Ca3(PO4)2] precipitation was used for improving the clarification efficiency in harvest process of the monoclonal antibody (mAb) containing cell culture fluid (CCF) with high turbidity and product titer. The flocculation conditions (concentration, addition order of flocculants, pH, and operation time), and the effect of flocculants on the mAb physical chemical properties (such as distribution of charge variants and aggregates) and process-related impurities removal (such as DNA and CHOP) were evaluated in this study...
May 2017: Bioprocess and Biosystems Engineering
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