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https://www.readbyqxmd.com/read/29213270/nanobodies-and-nanobody-based-human-heavy-chain-antibodies-as-antitumor-therapeutics
#1
REVIEW
Peter Bannas, Julia Hambach, Friedrich Koch-Nolte
Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29209322/camelid-single-domain-antibodies-historical-perspective-and-future-outlook
#2
Mehdi Arbabi-Ghahroudi
Tremendous effort has been expended over the past two and a half decades to understand many aspects of camelid heavy chain antibodies, from their biology, evolution, and immunogenetics to their potential applications in various fields of research and medicine. In this article, I present a historical perspective on the development of camelid single-domain antibodies (sdAbs or VHHs, also widely known as nanobodies) since their discovery and discuss the advantages and disadvantages of these unique molecules in various areas of research, industry, and medicine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29207143/screening-and-antitumor-effect-of-an-anti%C3%A2-ctla%C3%A2-4-nanobody
#3
Ruirong Wan, Aiqun Liu, Xiaoqiong Hou, Zongqiang Lai, Jieping Li, Nuo Yang, Juntao Tan, Fengzhen Mo, Zixi Hu, Xiaomei Yang, Yongxiang Zhao, Xiaoling Lu
Cytotoxic T‑lymphocyte antigen‑4 (CTLA‑4) is a critical negative regulator of immune responses. CTLA‑4 is rapidly upregulated following T‑cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA‑4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA‑4 activity for enhancing immune responses against cancer...
December 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29182399/application-of-camelid-heavy-chain-variable-domains-vhhs-in-prevention-and-treatment-of-bacterial-and-viral-infections
#4
Lucas Wilken, Anne McPherson
Camelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen-binding units to occur in nature. VHHs possess high degrees of solubility and robustness enabling generation of multivalent constructs with increased avidity - characteristics that mark their superiority to other antibody fragments and monoclonal antibodies. Capable of effectively binding to molecular targets inaccessible to classical immunotherapeutic agents and easily produced in microbial culture, VHHs are considered promising tools for pharmaceutical biotechnology...
November 28, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29181380/production-preservation-and-transfer-of-south-american-camelid-embryos
#5
REVIEW
Virginia L Trasorras, María Ignacia Carretero, Deborah M Neild, Maria Graciela Chaves, Susana M Giuliano, Marcelo H Miragaya
The current review summarizes progress in the field of in vitro and in vivo production of South American Camelid embryos. Both methods require ovarian superstimulation (with FSH and eCG) to obtain multiple ovulations (in vivo embryo production) or to induce follicle growth for oocyte collection (in vitro embryo production). Moreover, superstimulation entails prior administration of hormones that inhibit follicular growth (progesterone, progestagens, and estrogens). Cumulus-oocyte complexes obtained must mature in vivo (buserelin administration) or in vitro to then be subjected to in vitro fertilization or intracytoplasmic sperm injection...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29177623/expression-of-single-domain-antibody-in-different-systems
#6
REVIEW
Yongkang Liu, He Huang
Camelid single-domain antibodies (sdAbs, VHHs, or Nanobodies®) are types of antibody fragments that are composed of the heavy-chain variable domain only. These VHHs possess unique structural and functional features, as they are small in size and exhibit thermal stability and high solubility. Compared to conventional antibodies, VHHs can be manufactured in microorganisms to significantly save on cost, labor, and time since VHHs lack the Fc domain with its N-linked oligosaccharide. Until now, VHHs have been expressed in several kinds of production systems, ranging from prokaryotic cells, yeasts, fungi, insect cells, and mammalian cell lines, to plants...
November 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29163515/nanobody-based-delivery-systems-for-diagnosis-and-targeted-tumor-therapy
#7
REVIEW
Yaozhong Hu, Changxiao Liu, Serge Muyldermans
The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma's, monoclonal antibodies (mAbs) have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163485/a-novel-affinity-tag-abtag-and-its-application-to-the-affinity-screening-of-single-domain-antibodies-selected-by-phage-display
#8
Greg Hussack, Toya Nath Baral, Jason Baardsnes, Henk van Faassen, Shalini Raphael, Kevin A Henry, Jianbing Zhang, C Roger MacKenzie
ABTAG is a camelid single-domain antibody (sdAb) that binds to bovine serum albumin (BSA) with low picomolar affinity. In surface plasmon resonance (SPR) analyses using BSA surfaces, bound ABTAG can be completely dissociated from the BSA surfaces at low pH, over multiple cycles, without any reduction in the capacity of the BSA surfaces to bind ABTAG. A moderate throughput, SPR-based, antibody screening assay exploiting the unique features of ABTAG is described. Anti-carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) sdAbs were isolated from a phage-displayed sdAb library derived from the heavy chain antibody repertoire of a llama immunized with CEACAM6...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29156539/epidemiological-investigations-of-four-cowpox-virus-outbreaks-in-alpaca-herds-germany
#9
Almut Prkno, Donata Hoffmann, Daniela Goerigk, Matthias Kaiser, Anne Catherine Franscisca van Maanen, Kathrin Jeske, Maria Jenckel, Florian Pfaff, Thomas W Vahlenkamp, Martin Beer, Rainer G Ulrich, Alexander Starke, Martin Pfeffer
Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012-2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been described in South American camelids (SACs) only three times, all four herds were investigated to gain a deeper understanding of CPXV epidemiology in alpacas. The different herds were investigated twice, and various samples (serum, swab samples, and crusts of suspicious pox lesions, feces) were taken to identify additionally infected animals...
November 18, 2017: Viruses
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#10
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116505/construction-of-high-quality-camel-immune-antibody-libraries
#11
Ema Romão, Vianney Poignavent, Cécile Vincke, Christophe Ritzenthaler, Serge Muyldermans, Baptiste Monsion
Single-domain antibodies libraries of heavy-chain only immunoglobulins from camelids or shark are enriched for high-affinity antigen-specific binders by a short in vivo immunization. Thus, potent binders are readily retrieved from relatively small-sized libraries of 10(7)-10(8) individual transformants, mostly after phage display and panning on a purified target. However, the remaining drawback of this strategy arises from the need to generate a dedicated library, for nearly every envisaged target. Therefore, all the procedures that shorten and facilitate the construction of an immune library of best possible quality are definitely a step forward...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29110898/successful-pregnancies-from-vitrified-embryos-in-the-dromedary-camel-avoidance-of-a-possible-toxic-effect-of-sucrose-on-embryos
#12
M Herrid, M Billah, J A Skidmore
Successful embryo cryopreservation facilitates the wider application of assisted reproduction technologies and also provides a useful method for gene banking of valuable genetics. Unfortunately attempts to establish an effective cryopreservation protocol for camelid embryos have been unsuccessful. In the current study, a modified vitrification protocol with three steps was investigated, whereby embryos were exposed to solutions containing increasing amounts of glycerol and ethylene glycol for fixed time periods...
October 26, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/29061039/quantitatively-predictable-control-of-cellular-protein-levels-through-proteasomal-degradation
#13
Wenting Zhao, Lara Pferdehirt, Laura Segatori
Protein function is typically studied and engineered by modulating protein levels within the complex cellular environment. To achieve fast, targeted, and predictable control of cellular protein levels without genetic manipulation of the target, we developed a technology for post-translational depletion based on a bifunctional molecule (NanoDeg) consisting of the antigen-binding fragment from the Camelidae species heavy-chain antibody (nanobody) fused to a degron signal that mediates degradation through the proteasome...
November 7, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29054987/theranostic-radiolabeled-anti-cd20-sdab-for-targeted-radionuclide-therapy-of-non-hodgkin-lymphoma
#14
Ahmet Krasniqi, Matthias D'Huyvetter, Catarina Xavier, Kevin Van der Jeught, Serge Muyldermans, José Van Der Heyden, Tony Lahoutte, Jan Tavernier, Nick Devoogdt
Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAbs) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected based on its specific tumor targeting and significant lower kidney accumulation compared to other sdAbs...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29047203/engineered-cross-reacting-nanobodies-simplify-comparative-oncology-between-humans-and-dogs
#15
E Mazzega, A de Marco
Antibodies cross-reacting with homologue antigens in different species would be essential reagents for the development of comparative oncology studies. In comparison with conventional immunoglobulin Gs, recombinant nanobodies (single-domain variable regions of heavy-chain only antibodies of Camelidae origin) can be easily isolated in vitro and engineered into a variety of reagents with optimized characteristics for different research and clinical applications. We recovered an anti-human epidermal growth factor receptor 2 (anti-HER2) nanobody from a naïve llama library by direct panning on whole cells and expressed it fused to Fc and green fluorescent protein...
October 18, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29045695/a-new-collection-of-amblyomma-parvitarsum-acari-ixodidae-in-peru-with-description-of-a-gynandromorph-and-report-of-rickettsia-detection
#16
S Muñoz-Leal, T F Martins, L R Luna, A Rodriguez, M B Labruna
Adult stages of Amblyomma parvitarsum Neumann parasitize wild and domestic camelids of the genera Lama and Vicugna in highlands of Andean Plateau and Patagonia. Within the Peruvian Andes, few reports have documented this tick-host association, and although reported in Chile and Argentina, Rickettsia-infected A. parvitarsum remains undocumented for this country. Here we report a new collection of A. parvitarsum from Peru, the finding of the first gynandromorph for the species and high prevalence of Rickettsia in adult stages...
October 17, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/29042015/identification-of-monoclonal-antibodies-cross-reactive-with-bottlenose-dolphin-orthologues-of-the-major-histocompatibility-complex-and-leukocyte-differentiation-molecules
#17
Mahmoud M Elnaggar, Gaber S Abdellrazeq, Stephanie K Venn-Watson, Eric D Jensen, Victoria Hulubei, Lindsay M Fry, Randy E Sacco, William C Davis
The slow progress in understanding immunotoxic effects of environmental contaminants and their influence on disease susceptibility in whales is largely due to the limited information available on the immune systems and immune function of species included in the Cetancodontamorpha clade. Studies in species in the other major clades included in the Artiodactylamorpha, Ruminantiamorpha, Suinamorpha, and Camelidamorpha have revealed the immune systems are similar, but not identical. The present study was undertaken to expand the available monoclonal antibody reagents needed to gain insight into the composition, function, and evolution of the immune system in Cetancodontamorpha, using the dolphin (Tursiops truncatus) as a model cetacean species...
October 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29041922/institute-collection-and-analysis-of-nanobodies-ican-a-comprehensive-database-and-analysis-platform-for-nanobodies
#18
Jing Zuo, Jian Li, Rongxin Zhang, Longsheng Xu, Hanhan Chen, Xiaohuan Jia, Zhipeng Su, Linhong Zhao, Xing Huang, Wei Xie
BACKGROUND: Nanobodies are single-domain antibodies that contain the unique structural and functional properties of naturally-occurring heavy chain in camelidae. As a novel class of antibody, they show many advantages compared with traditional antibodies such as smaller size, higher stability, improved specificity, more easily expressed in microorganisms. These unusual hallmarks make them as promising tools in basic research and clinical practice. Although thousands of nanobodies are known to be published, no single database provides searchable, unified annotation and integrative analysis tools for these various nanobodies...
October 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29039819/single-domain-antibodies-as-new-biomarker-detectors
#19
REVIEW
Chiuan Herng Leow, Katja Fischer, Chiuan Yee Leow, Qin Cheng, Candy Chuah, James McCarthy
Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms...
October 17, 2017: Diagnostics
https://www.readbyqxmd.com/read/29031230/astatine-211-labeled-anti-her2-5f7-single-domain-antibody-fragment-conjugates-radiolabeling-and-preliminary-evaluation
#20
Jaeyeon Choi, Ganesan Vaidyanathan, Eftychia Koumarianou, Choong Mo Kang, Michael R Zalutsky
INTRODUCTION: Derived from heavy chain only camelid antibodies, ~15-kDa single-domain antibody fragments (sdAbs) are an attractive platform for developing molecularly specific imaging probes and targeted radiotherapeutics. The rapid tumor accumulation and normal tissue clearance of sdAbs might be ideal for use with (211)At, a 7.2-h half-life α-emitter, if appropriate labeling chemistry can be devised to trap (211)At in cancer cells after sdAb binding. This study evaluated two reagents, [(211)At]SAGMB and iso-[(211)At]SAGMB, for this purpose...
September 19, 2017: Nuclear Medicine and Biology
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