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Antibody engineering

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https://www.readbyqxmd.com/read/28921443/polyester-based-nanoparticles-for-the-encapsulation-of-monoclonal-antibodies
#1
Flávia Sousa, Pedro Fonte, Andreia Cruz, Patrick J Kennedy, Inês Mendes Pinto, Bruno Sarmento
Aliphatic polyesters have been widely explored for biomedical applications (e.g., drug delivery systems, biomedical devices, and tissue engineering). Recently, polyesters have been used in nanoparticle formulations for the controlled release of monoclonal antibodies (mAbs) for the enhanced efficacy of antibody-based therapy. Polyester-based nanoparticles for mAb delivery provide decreased antibody dosage, increased antibody stability and protection and longer therapeutic action, ultimately translating to an increased therapeutic index...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28919443/fv-clasp-an-artificially-designed-small-antibody-fragment-with-improved-production-compatibility-stability-and-crystallizability
#2
Takao Arimori, Yu Kitago, Masataka Umitsu, Yuki Fujii, Ryoko Asaki, Keiko Tamura-Kawakami, Junichi Takagi
Antibody fragments are frequently used as a "crystallization chaperone" to aid structural analysis of complex macromolecules that are otherwise crystallization resistant, but conventional fragment formats have not been designed for this particular application. By fusing an anti-parallel coiled-coil structure derived from the SARAH domain of human Mst1 kinase to the variable region of an antibody, we succeeded in creating a novel chimeric antibody fragment of ∼37 kDa, termed "Fv-clasp," which exhibits excellent crystallization compatibility while maintaining the binding ability of the original IgG molecule...
September 6, 2017: Structure
https://www.readbyqxmd.com/read/28916265/glycans-function-as-anchors-for-antibodies-and-help-drive-hiv-broadly-neutralizing-antibody-development
#3
Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S Shivatare, Bryan Briney, James E Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R Burton
Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain...
September 8, 2017: Immunity
https://www.readbyqxmd.com/read/28915385/photoluminescent-lateral-flow-based-on-non-radiative-energy-transfer-for-protein-detection-in-human-serum
#4
Alejandro Zamora-Gálvez, Eden Morales-Narváez, Javier Romero, Arben Merkoçi
A new paper-based lateral flow immunoassay configuration was engineered and investigated. The assay is intended for the detection of a model protein in human serum, that is, human immunoglobulin G, with the aim to demonstrate a virtually universal protein detection platform. Once the sample is added in the strip, the analyte is selectively captured by antibody-decorated silica beads (Ab-SiO2) onto the conjugate pad and the sample flows by capillarity throughout the strip until reaching the test line, where a sandwich-like immunocomplex takes place due to the presence of antibody-functionalized QDs (Ab-QDs) onto the test line...
September 11, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#5
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28906588/surface-glycan-pattern-of-canine-equine-and-ovine-bone-marrow-derived-mesenchymal-stem-cells
#6
Salvatore Desantis, Gianluca Accogli, Antonio Crovace, Edda G Francioso, Alberto Maria Crovace
The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin...
September 14, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28902916/targeted-n-glycan-deletion-at-the-receptor-binding-site-retains-hiv-env-nfl-trimer-integrity-and-accelerates-the-elicited-antibody-response
#7
Viktoriya Dubrovskaya, Javier Guenaga, Natalia de Val, Richard Wilson, Yu Feng, Arlette Movsesyan, Gunilla B Karlsson Hedestam, Andrew B Ward, Richard T Wyatt
Extensive shielding by N-glycans on the surface of the HIV envelope glycoproteins (Env) restricts B cell recognition of conserved neutralizing determinants. Elicitation of broadly neutralizing antibodies (bNAbs) in selected HIV-infected individuals reveals that Abs capable of penetrating the glycan shield can be generated by the B cell repertoire. Accordingly, we sought to determine if targeted N-glycan deletion might alter antibody responses to Env. We focused on the conserved CD4 binding site (CD4bs) since this is a known neutralizing determinant that is devoid of glycosylation to allow CD4 receptor engagement, but is ringed by surrounding N-glycans...
September 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28901971/xenotransplantation-past-present-and-future
#8
Burcin Ekser, Ping Li, David K C Cooper
PURPOSE OF REVIEW: To review the progress in the field of xenotransplantation with special attention to most recent encouraging findings which will eventually bring xenotransplantation to the clinic in the near future. RECENT FINDINGS: Starting from early 2000, with the introduction of galactose-α1,3-galactose (Gal)-knockout pigs, prolonged survival especially in heart and kidney xenotransplantation was recorded. However, remaining antibody barriers to non-Gal antigens continue to be the hurdle to overcome...
September 8, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28901715/engineering-microbial-metabolite-dynamics-and-heterogeneity
#9
REVIEW
Alexander C Schmitz, Christopher J Hartline, Fuzhong Zhang
Monoclonal antibodies currently dominate the biopharmaceutical market with growing sales having reached 80 billion USD in 2016. As most top-selling mAbs are approaching the end of their patent life, biopharmaceutical companies compete fiercely in the biosimilars market. These two factors present a strong motivation for alternative process strategies and process optimization. In this work a novel purification strategy for monoclonal antibodies comprising phenylboronic acid multimodal chromatography for capture followed by polishing by ion exchange monolithic chromatography and packed bed hydrophobic interaction chromatography is presented and compared to the traditional protein-A-based process...
September 13, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28901254/therapeutics-and-immunoprophylaxis-against-noroviruses-and-rotaviruses
#10
Souvik Ghosh, Yashpal Singh Malik, Nobumichi Kobayashi
Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of non-bacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea. Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses, so far. On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials...
September 12, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28900504/platelet-targeted-delivery-of-peripheral-blood-mononuclear-cells-to-the-ischemic-heart-restores-cardiac-function-after-ischemia-reperfusion-injury
#11
Melanie Ziegler, Xiaowei Wang, Bock Lim, Ephraem Leitner, Franco Klingberg, Victoria Ching, Yu Yao, Dexing Huang, Xiao-Ming Gao, Helen Kiriazis, Xiao-Jun Du, Jody J Haigh, Alex Bobik, Christoph E Hagemeyer, Ingo Ahrens, Karlheinz Peter
One of the major hurdles in intravenous regenerative cell therapy is the low homing efficiency to the area where these cells are needed. To increase cell homing toward areas of myocardial damage, we developed a bispecific tandem single-chain antibody (Tand-scFvSca-1+GPIIb/IIIa) that binds with high affinity to activated platelets via the activated glycoprotein (GP)IIb/IIIa receptor, and to a subset of peripheral blood mononuclear cells (PBMC) which express the stem cell antigen-1 (Sca-1) receptor. Methods: The Tand-scFvSca-1+GPIIb/IIIa was engineered, characterized and tested in a mouse model of ischemia-reperfusion (IR) injury applying left coronary artery occlusion for 60 min...
2017: Theranostics
https://www.readbyqxmd.com/read/28900185/anti-a%C3%AE-single-chain-variable-fragment-antibodies-restore-memory-acquisition-in-a-drosophila-model-of-alzheimer-s-disease
#12
Alfonso Martin-Peña, Diego E Rincon-Limas, Pedro Fernandez-Funez
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder triggered by the accumulation of soluble assemblies of the amyloid-β42 (Aβ42) peptide. Despite remarkable advances in understanding the pathogenesis of AD, the development of palliative therapies is still lacking. Engineered anti-Aβ42 antibodies are a promising strategy to stall the progression of the disease. Single-chain variable fragment (scFv) antibodies increase brain penetration and offer flexible options for delivery while maintaining the epitope targeting of full antibodies...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899628/a-novel-approach-to-a-rabies-vaccine-based-on-a-recombinant-single-cycle-flavivirus-vector
#13
Maryann Giel-Moloney, Alexander A Rumyantsev, Fred David, Monica Figueiredo, Brad Feilmeier, Teshome Mebatsion, Mark Parrington, Harry Kleanthous, Konstantin V Pugachev
The RepliVax® vaccine (RV) platform is based on flavivirus genomes that are rationally attenuated by deletion. These single-cycle RV vaccine candidates targeting flavivirus pathogens have been demonstrated to be safe, highly immunogenic, and efficacious in animal models, including non-human primates. Here we show utility of the technology for delivery of a non-flavivirus immunogen by engineering several West Nile-based RV vectors to express full-length rabies virus G protein. The rabies virus G protein gene was incorporated in place of different West Nile structural protein gene deletions...
September 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28898398/integrating-high-throughput-screening-and-sequencing-for-monoclonal-antibody-discovery-and-engineering
#14
REVIEW
Cristina Parola, Daniel Neumeier, Sai T Reddy
Monoclonal antibody discovery and engineering is a field that has traditionally been dominated by high-throughput screening platforms (e.g., hybridomas and surface display). In recent years the emergence of high-throughput sequencing has made it possible to obtain large-scale information on antibody repertoire diversity. Additionally, it has now become more routine to perform high-throughput sequencing on antibody repertoires to also directly discover antibodies. In this review, we provide an overview of the progress in this field to date and show how high-throughput screening and sequencing are converging to deliver powerful new workflows for monoclonal antibody discovery and engineering...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28895854/gene-therapy-approaches-to-human-immunodeficiency-virus-and-other-infectious-diseases
#15
REVIEW
Geoffrey L Rogers, Paula M Cannon
Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28893099/obinutuzumab-for-the-treatment-of-chronic-lymphocytic-leukemia-and-other-b-cell-lymphoproliferative-disorders
#16
Rabih Said, Apostolia M Tsimberidou
Chemoimmunotherapeutic regimens using the anti-CD20 antibody rituximab improved significantly the survival rates in various B-cell lymphoproliferative disorders (LPDs), including chronic lymphocytic leukemia (CLL). The next-generation CD20 antibody obinutuzumab represents an addition to the drug armamentarium used for the therapeutic management of patients with LPDs. Areas covered: Herein, the authors discuss the biochemical and conformational engineering of obinutuzumab to increase antibody-dependent cell-mediated cytotoxicity and direct cell death...
September 11, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28892050/carcinoembryonic-antigen-related-cell-adhesion-molecule-6-ceacam6-promotes-egf-receptor-signaling-of-oral-squamous-cell-carcinoma-metastasis-via-the-complex-n-glycosylation
#17
W-F Chiang, T-M Cheng, C-C Chang, S-H Pan, C A Changou, T-H Chang, K-H Lee, S-Y Wu, Y-F Chen, K-H Chuang, D-B Shieh, Y-L Chen, C-C Tu, W-L Tsui, M-H Wu
Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28891272/synthetic-modular-antibody-construction-using-the-spytag-spycatcher-protein-ligase-system
#18
Md Kausar Alam, Carolina Gonzalez, Wayne Hill, Humphrey Fonge, Kris Barreto, Clarence Ronald Geyer
Efforts to engineer recombinant antibodies for specific diagnostic and therapy applications are time consuming and expensive as each new recombinant antibody needs to be optimized for expression, stability, bio-distribution, and pharmacokinetics. We developed a new way to construct recombinant antibody-like "devices" using a "bottom up" approach to build them from well-behaved discrete recombinant antibody domains or "parts". Studies on antibody structure and function have identified antibody constant and variable domains with specific functions that can be expressed in isolation...
September 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28890351/in-situ-delivery-and-production-system-of-trastuzumab-scfv-with-bifidobacterium
#19
Takeshi Kikuchi, Hitomi Shimizu, Yasuto Akiyama, Shun'ichiro Taniguchi
A monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2), trastuzumab has become a standard treatment for HER2-positive breast cancer. Recent advancements in antibody engineering have enabled the efficient generation of the trastuzumab single-chain variable fragment (scFv). In this study, we genetically engineered Bifidobacterium, a bacterial strain shown to accumulate safely and selectively in hypoxic tumor sites by intravenous (iv) injection, to express and secrete the trastuzumab scFv...
September 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28888210/antibody-cytokine-fusion-proteins-for-improving-efficacy-and-safety-of-cancer-therapy
#20
REVIEW
Zahra Valedkarimi, Hadi Nasiri, Leili Aghebati-Maleki, Jafar Majidi
Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules...
September 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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