共查询到20条相似文献,搜索用时 15 毫秒
1.
Smith MD 《Biotechnology advances》1996,14(3):267-281
Production of heterologous proteins in plants has become increasingly efficient due to recent advances in plant biotechnology. Heterologous proteins that have specifically attracted a great deal of attention are plant-produced monoclonal antibodies. A variety of applications for these so-called plantibodies have been explored since they were first expressed in tobacco seven years ago. Both full length antibodies and antibody fragments produced in transgenic plants offer many intriguing possibilities to plant molecular biologists and plant breeders. However, questions such as how cellular targeting influences the expression and accumulation of these proteins in plants still need to be answered before the technology can be used commercially, on a large-scale. 相似文献
2.
Monoclonal antibodies (Mabs) have been used as diagnostic and analytical reagents since hybridoma technology was invented
in 1975. In recent years, antibodies have become increasingly accepted as therapeutics for human diseases, particularly for
cancer, viral infection and autoimmune disorders. An indication of the emerging significance of antibody-based therapeutics
is that over a third of the proteins currently undergoing clinical trials in the United States are antibodies. Until the late
1980's, antibody technology relied primarily on animal immunization and the expression of engineered antibodies. However,
the development of methods for the expression of antibody fragments in bacteria and powerful techniques for screening combinatorial
libraries, together with the accumulating structure-function data base of antibodies, have opened unlimited opportunities
for the engineering of antibodies with tailor-made properties for specific applications. Antibodies of low immunogenicity,
suitable for human therapy andin vivo diagnosis, can now be developed with relative ease. Here, antibody structure-function and antibody engineering technologies
are described. 相似文献
3.
Boder ET Raeeszadeh-Sarmazdeh M Price JV 《Archives of biochemistry and biophysics》2012,526(2):99-106
Since its first application to antibody engineering 15years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering. 相似文献
4.
It has been more than 50 years since antinuclear antibodies were first discovered and found to be associated with connective tissue diseases. Since then different methods have been described and used for their detection or confirmation. For many decades immunofluorescent antinuclear antibody test has been the "gold standard" in the diagnosis of these disorders. However to increase the sensitivity and specificity of antinuclear antibody detection further approaches were explored. Today a battery of newer techniques are available some of which are now considered better and are competing with the older methods. This article provides an overview on advancement in antinuclear antibody detection methods, their future prospects, advantages, disadvantages and guidelines for use of these tests. 相似文献
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The number and types of antibodies expressed in plants has increased steadily since the first reports of this accomplishment in the 1980s, illustrating the versatility of plants as a production system for antibodies. Many recent reviews have detailed the antibody forms that have been derived from plant expression systems. This contribution focuses on the remaining challenges to develop plant-derived therapeutic antibodies into products, and some of the progress that is being made in addressing these challenges. 相似文献
7.
Okamoto T Mukai Y Yoshioka Y Shibata H Kawamura M Yamamoto Y Nakagawa S Kamada H Hayakawa T Mayumi T Tsutsumi Y 《Biochemical and biophysical research communications》2004,323(2):583-591
Monoclonal antibodies (MAbs) are widely applied in basic research, medicine, and the pharmaceutical industry. Recently, applications and generations of MAbs have been increasingly attracting attention in many research areas since MAbs could be produced in large quantities with the development of genetic technology and antibody engineering. On the other hand, in recent years, phage display system has been developed for high-throughput isolation and generation of novel MAbs that have high affinity with various antigens. This technology is capable of constructing "Library" containing billions of phage repertoires displaying various antibody fragments, and rapid selection of a specific MAb from this phage library. Additionally, this technology has a great advantage that MAbs can be generated without immunization to animals. However, there are still relatively few reports confirming that useful MAbs can be derived from non-immune antibody libraries. The latter, as undertaken by current methods, seem unable to achieve the high quality required to produce useful MAbs for any desired antigen because cloning of antibody gene from non-immune donors is inefficient. This problem is caused by the fact that their RT-PCR primer sets, PCR conditions, and efficiency of subcloning through construction of antibody gene library cannot encompass all the antibody diversity. In an attempt to overcome some of these earlier problems, here we describe an optimized method to establish a high quality, non-immune library from mouse bone-marrow and spleen, and assess its diversity in terms of content of multiple antibodies for a wide antigenic repertoire. As an example of the application of the methodology, we describe the selection of specific MAbs binding to Luciferase and identify at least 18 different clones. Using this non-immune mouse antibody library, we also obtained MAbs for VEGF, VEGF receptor 2, TNF-alpha, and Pseudomonas Exotoxin, confirming the high quality of the library and its suitability for this application. 相似文献
8.
A compact phage display human scFv library for selection of antibodies to a wide variety of antigens 总被引:1,自引:0,他引:1
Potjamas Pansri Nanthnit Jaruseranee Kuntalee Rangnoi Peter Kristensen Montarop Yamabhai 《BMC biotechnology》2009,9(1):6-16
Background
Phage display technology is a powerful new tool for making antibodies outside the immune system, thus avoiding the use of experimental animals. In the early days, it was postulated that this technique would eventually replace hybridoma technology and animal immunisations. However, since this technology emerged more than 20 years ago, there have only been a handful reports on the construction and application of phage display antibody libraries world-wide. 相似文献9.
In the last few years, fluorescence polarization (FP) has been applied to the development of robust, homogeneous, high throughput assays in molecular recognition research, such as ligand-protein interactions. Recently, this technology has been applied to the development of homogeneous tyrosine kinase assays, since there are high-affinity anti-phosphotyrosine antibodies available. Unlike tyrosine kinases, application of FP to assay development for serine/threonine kinases has been impeded because of lack of high-affinity anti-phosphoserine/threonine antibodies. In the present study, we report the discovery of a high-affinity, monoclonal anti-phosphoserine antibody, 2B9, with a Kd of 250 +/- 34 pM for a phosphoserine-containing peptide tracer, fluorescein-RFARKGS(PO(4))LRQKNV. Our data suggest that 2B9 is selective for fluorescein-RFARKGS(PO(4))LRQKNV. The antibody and tracer have been used for the development of a competitive FP assay for protein kinase C (PKC) in 384-well plates. Phosphatidylserine, which enhances the kinase activity of PKC in a Ca(2+)-dependent manner and has a structure similar to that of phosphoserine, did not interfere with binding of the peptide tracer to the antibody in the FP assay. The data indicate that the FP assay is more sensitive and robust than the scintillation proximity assay for PKC. The FP assay developed here can be used for rapid screening of hundreds of thousands of compounds for discovery of therapeutic leads for PKC-related diseases. 相似文献
10.
Cohn M Mitchison NA Paul WE Silverstein AM Talmage DW Weigert M 《Nature reviews. Immunology》2007,7(10):823-830
How do we account for the immune system's ability to produce antibodies in response to new antigens? It has been 50 years since F. Macfarlane Burnet published his answer to this question: the clonal-selection theory of antibody diversity. The idea that specificity for diverse antigens exists before these antigens are encountered was a radical notion at the time, but one that became widely accepted. In this article, Nature Reviews Immunology asks six key scientists for their thoughts and opinions on the clonal-selection theory, from its first proposal to their views of it today. 相似文献
11.
Soomin Yoon Yong-Sung Kim Hyunbo Shim Junho Chung 《Biotechnology and Bioprocess Engineering》2010,15(5):709-715
Since the first monoclonal antibody, muromonab-CD3, was approved for therapeutic use in 1986, numerous molecules have been
targeted using therapeutic antibody technology, resulting in 26 therapeutic antibodies being approved by the US FDA as of
November, 2009. Initial concerns regarding antibody drugs focused on immunogenicity, short serum half-life, and weak efficacy.
As the types of antibodies progressed from murine to chimeric, humanized, and fully human antibodies, great progress has been
made in immunogenicity and in vivo instability issues. For example, humanized antibodies, such as bevacizumab, exhibit less than 0.2% immunogenicity and a 20
day serum half-life, which is comparable to native immunoglobulin. Some recently developed antibodies are exceedingly efficacious
and have become first-line therapy for their target diseases. Here, we address and analyze all clinically approved therapeutic
antibodies to date by discussing immunogenicity, half-life, and efficacy. 相似文献
12.
It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge. 相似文献
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14.
Rader C Ritter G Nathan S Elia M Gout I Jungbluth AA Cohen LS Welt S Old LJ Barbas CF 《The Journal of biological chemistry》2000,275(18):13668-13676
The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nm range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen. 相似文献
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16.
Polyclonal antibody therapy in the form of hyper-immune serum has for more than a century been used for treatment of many
infectious diseases. However, with the emergence of first antibiotics and later recombinant monoclonal antibody therapy, the
use of hyper-immune serum has declined. The main reason for this is that methods for consistent manufacturing of safe hyper
immune immunoglobulin products have been lacking. In contrast, manufacturing processes of recombinant monoclonal antibodies
follow a well established schedule and it appears obvious to use similar methods to produce recombinant polyclonal products.
However, the methods for monoclonal antibody manufacturing are, for several reasons, not directly applicable to generation
and manufacture of polyclonal recombinant antibodies. A new production strategy based on recombinant mammalian producer cells
has recently been developed to support consistent generation of recombinant polyclonal antibodies for therapeutic use. This
review describes aspects of this novel technology with emphasis on the generation, production and characterization procedures
employed, and provides comparison with alternative polyclonal and monoclonal antibody manufacturing strategies. 相似文献
17.
More than 10 years have now elapsed since the first reports confirmed that antibodies could be programmed as catalysts for
chemical processes. Much of the initial research focussed on exploring the scope and utility of these new biocatalysts. Recently
however, increasing information gleaned from X-ray analyses is allowing an exciting insight into the structural basis of antibody
catalyzed reactions. This review details the evolving knowledge of the structure-function relationship for catalytic antibodies
that accelerate a range of different reaction classes. 相似文献
18.
After the appearance of the first FDA-approved antibody 25 years ago, antibodies have become major therapeutic agents in the treatment of many human diseases, including cancer and infectious diseases, and the use of antibodies as therapeutic/diagnostic agents is expected to increase in the future. So far, a variety of strategies have been devised for engineering of these fascinating molecules to develop superior properties and functions. Recent progress in systems biology has provided more information about the structures and cellular networks of antibodies, and, in addition, recent development of biotechnology tools, particularly in regard to high-throughput screening, has made it possible to perform more intensive engineering on these substances. Based on a sound understanding and new technologies, antibodies are now being developed as more powerful drugs. In this review, we highlight the recent, significant progress that has been made in antibody engineering, with a particular focus on Fc engineering and glycoengineering for improved functions, and cellular engineering for enhanced production of antibodies in yeast and bacterial hosts. 相似文献
19.
In recent years, several cell-based screening technologies for the isolation of antibodies with prescribed properties emerged. They rely on the multi-copy display of antibodies or antibody fragments on a cell surface in functional form followed by high through put screening and isolation of cell clones that carry an antibody variant with the desired affinity, specificity, and stability. Particularly yeast surface display in combination with high-throughput fluorescence-activated cell sorting has proven successful in the last fifteen years as a very powerful technology that has some advantages over classical generation of monoclonals using the hybridoma technology or bacteriophage-based antibody display and screening. Cell-based screening harbours the benefit of single-cell online and real-time analysis and characterisation of individual library candidates. Moreover, when using eukaryotic expression hosts, intrinsic quality control machineries for proper protein folding and stability exist that allow for co-selection of high-level expression and stability simultaneously to the binding functionality. Recently, promising technologies emerged that directly rely on antibody display on higher eukaryotic cell lines using lentiviral transfection or direct screening on B-cells. The combination of immunisation, B-cell screening and next generation sequencing may open new avenues for the isolation of therapeutic antibodies with prescribed physicochemical and functional characteristics. 相似文献
20.
Design of humanized antibodies: from anti-Tac to Zenapax 总被引:3,自引:0,他引:3
Since the introduction of hybridoma technology, monoclonal antibodies have become one of the most important tools in the biosciences, finding diverse applications including their use in the therapy of human disease. Initial attempts to use monoclonal antibodies as therapeutics were hampered, however, by the potent immunogenicity of mouse (and other rodent) antibodies in humans. Humanization technology has made it possible to remove the immunogenicity associated with the use of rodent antibodies, or at least to reduce it to an acceptable level for clinical use in humans, thus facilitating the application of monoclonal antibodies to the treatment of human disease. To date, nine humanized monoclonal antibodies have been approved for use as human therapeutics in the United States. In this paper, we describe procedures for antibody humanization with an emphasis on strategies for designing humanized antibodies with the aid of computer-guided modeling of antibody variable domains, using as an example the humanized anti-CD25 monoclonal antibody, Zenapax. 相似文献