 |
|
First production of human monoclonal antibodies in chicken eggs published in Nature Biotechnology
August 29, 2005Chicken-produced antibodies demonstrate enhanced cell killing compared to conventionally produced anti-cancer antibodies
BURLINGAME, CA (August 29, 2005): Origen Therapeutics today announced the first published scientific report of fully functional, human sequence monoclonal antibodies (mAbs) produced in chickens. The antibodies were expressed solely in the chicken oviduct and deposited into egg white in concentrations of 1-3 milligrams per egg. Moreover, antibodies produced in this manner demonstrated 10-100 fold greater cell-killing ability (ADCC) compared to therapeutic antibodies produced by conventional cell culture methods.
The new report was published in the September issue of Nature Biotechnology by researchers from Origen Therapeutics and their collaborators at Medarex, Texas A&M University and the University of California, Los Angeles. A research brief commenting on the potential impact of this development for the production of human therapeutic proteins was also published in the September issue of Nature Medicine.
"This work demonstrates the potential for producing therapeutic proteins with enhanced properties in the eggs of chickens as an alternative to established mammalian cell culture systems," said Robert J. Etches, Ph.D., D. Sc., Origen Therapeutics vice president, research. "Antibodies produced by this method had very similar physical and biological characteristics to those produced in CHO cells, including nearly identical binding curves, similar affinities, and an equal ability to be internalized by antigen on prostate cancer cells. At the same time, chicken-produced antibodies lacked the sugar residue, fucose, which greatly increases their cell-killing activity compared to CHO-produced antibodies."
To create the antibody-producing chickens, the researchers first inserted into chicken embryonic stem cells the genes encoding the antibody and the regulatory sequences restricting its deposition to egg white. The stem cells were then introduced into chick embryos. At this stage of development, the embryonic stem cells can make significant contributions to the developing chicken. Resulting chimeras with large contributions from the stem cells lay eggs containing milligram amounts of antibody, which is then separated from the egg white proteins generating the purified product.
"This work represents a considerable advance over past efforts to develop avian transgenes, which were limited to the insertion of only small pieces of DNA," commented Dr. Etches. "The technology described here is a general method for inserting DNA encoding proteins of essentially any size and complexity while achieving high levels of protein expression. Moreover, it is the only technology to date that restricts deposition of the therapeutic protein to egg white."
"Monoclonal antibodies have demonstrated great success as human therapeutics, with over 25 approved for human therapeutic use and an increasing number of these proteins in clinical development," continued Dr. Etches. "We expect the demand for more potent anti-cancer monoclonal antibodies and for lower production costs to increase at a rate that will tax existing cell culture production systems. The introduction of this new chicken-based production technology will be of considerable interest to an industry coping with the commercial supply of an ever increasing number of therapeutic antibodies."
"We believe the chicken system is an attractive one for therapeutic protein production compared to either plant systems or to other transgenic animal systems," said Robert Kay, Ph.D., Origen Therapeutics president and chief executive officer. "The fact that the chicken-produced anti-cancer antibodies show dramatically enhanced cell killing activity elevates the chicken system considerably relative to other non-traditional production technologies and some traditional cell culture methods as well."
"Furthermore," Dr. Kay continued, "unlike other transgenic animal systems, the time from antibody identification to production in eggs can be as short as 8 months versus 18 months to 3 years for goats or cattle. The egg is sterile and stable, providing a good starting material for isolation and purification of the protein of interest. Moreover, conditions for good manufacturing practices have been long-established for vaccine production in chicken eggs."
"This work really exemplifies the spirit of our Small Business Innovation Research grant program," said Matthew E. Portnoy, Ph.D., program director at the National Institute of General Medical Sciences at the National Institutes of Health. "This new technology has the potential to drive down drug manufacturing costs, which could make medicines and health insurance plans less expensive for all of us."
Kureczka/Martin Associates
"This work demonstrates the potential for producing therapeutic proteins with enhanced properties in the eggs of chickens as an alternative to established mammalian cell culture systems," said Robert J. Etches, Ph.D., D. Sc., Origen Therapeutics vice president, research. "Antibodies produced by this method had very similar physical and biological characteristics to those produced in CHO cells, including nearly identical binding curves, similar affinities, and an equal ability to be internalized by antigen on prostate cancer cells. At the same time, chicken-produced antibodies lacked the sugar residue, fucose, which greatly increases their cell-killing activity compared to CHO-produced antibodies."
To create the antibody-producing chickens, the researchers first inserted into chicken embryonic stem cells the genes encoding the antibody and the regulatory sequences restricting its deposition to egg white. The stem cells were then introduced into chick embryos. At this stage of development, the embryonic stem cells can make significant contributions to the developing chicken. Resulting chimeras with large contributions from the stem cells lay eggs containing milligram amounts of antibody, which is then separated from the egg white proteins generating the purified product.
"This work represents a considerable advance over past efforts to develop avian transgenes, which were limited to the insertion of only small pieces of DNA," commented Dr. Etches. "The technology described here is a general method for inserting DNA encoding proteins of essentially any size and complexity while achieving high levels of protein expression. Moreover, it is the only technology to date that restricts deposition of the therapeutic protein to egg white."
"Monoclonal antibodies have demonstrated great success as human therapeutics, with over 25 approved for human therapeutic use and an increasing number of these proteins in clinical development," continued Dr. Etches. "We expect the demand for more potent anti-cancer monoclonal antibodies and for lower production costs to increase at a rate that will tax existing cell culture production systems. The introduction of this new chicken-based production technology will be of considerable interest to an industry coping with the commercial supply of an ever increasing number of therapeutic antibodies."
"We believe the chicken system is an attractive one for therapeutic protein production compared to either plant systems or to other transgenic animal systems," said Robert Kay, Ph.D., Origen Therapeutics president and chief executive officer. "The fact that the chicken-produced anti-cancer antibodies show dramatically enhanced cell killing activity elevates the chicken system considerably relative to other non-traditional production technologies and some traditional cell culture methods as well."
"Furthermore," Dr. Kay continued, "unlike other transgenic animal systems, the time from antibody identification to production in eggs can be as short as 8 months versus 18 months to 3 years for goats or cattle. The egg is sterile and stable, providing a good starting material for isolation and purification of the protein of interest. Moreover, conditions for good manufacturing practices have been long-established for vaccine production in chicken eggs."
"This work really exemplifies the spirit of our Small Business Innovation Research grant program," said Matthew E. Portnoy, Ph.D., program director at the National Institute of General Medical Sciences at the National Institutes of Health. "This new technology has the potential to drive down drug manufacturing costs, which could make medicines and health insurance plans less expensive for all of us."
Kureczka/Martin Associates
Antibodies Current Events and Antibodies News RSSVaccine and drug research aimed at ticks and mosquitoes to prevent disease transmission
Most successful vaccines and drugs rely on protecting humans or animals by blocking certain bacteria from growing in their systems. But, a new theory actually hopes to take stopping infectious diseases such as West Nile virus and Malaria to the next level by disabling insects from transmitting these viruses.
Pediatric obesity may alter thyroid function and structure
In addition to its strong associations with hypertension, cardiovascular disease, and diabetes, pediatric obesity may induce alterations in thyroid function and structure, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Stanford blood scanner detects even faint indicators of cancer
A team led by Stanford researchers has developed a prototype blood scanner that can find cancer markers in the bloodstream in early stages of the disease, potentially allowing for earlier treatment and dramatically improved chances of survival.
CSHL scientists discover a new way in which epigenetic information is inherited
Hereditary information flows from parents to offspring not just through DNA but also through the millions of proteins and other molecules that cling to it.
New study indicates smallpox vaccination effective for decades
Although naturally occurring smallpox was eradicated in 1977, there is concern that bioterrorists might obtain smallpox from a laboratory and release it into the population.
Synthetic virus supports a bat origin for SARS
SARS - severe acute respiratory syndrome - alarmed the world five years ago as the first global pandemic of the 21st century. The coronavirus (SARS-CoV) that sickened more than 8,000 people - and killed nearly 800 of them - may have originated in bats, but the actual animal source is not known.
Nature Medicine study shows Peregrine's bavituximab can cure lethal virus infections
Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) today reported publication of data in Nature Medicine that supports the broad anti-viral potential of the company's novel anti-phosphatidylserine (anti-PS) antibody platform, showing that its PS-targeting drug bavituximab can cure lethal virus infections in animal disease models.
Adult stem cell breakthrough
The first tissue-engineered trachea (windpipe), utilising the patient's own stem cells, has been successfully transplanted into a young woman with a failing airway. The bioengineered trachea immediately provided the patient with a normally functioning airway, thereby saving her life.
Researchers aim to over-stress already taxed mantle cell lymphoma cells
Cancer cells are already stressed by the fast pace they require to grow and spread and scientists believe a little more stress just may kill them.
First trial of gene therapy for advanced heart failure shows promising results
Phase I results of the first clinical trial of gene therapy for patients with advanced heart failure show the approach to be promising, with improvements in several measures of the condition's severity.
More Antibodies Current Events and Antibodies News Articles
 | Antibodies: A Laboratory Manual by Ed Harlow, David Lane Introduction to immunochemistry for molecular biologists and other nonspecialists.... |
 | Antibody Engineering: Methods and Protocols (Methods in Molecular Biology) Univ. of Cambridge, UK. Presents cutting-edge techniques for the generation and optimization of recombinant antibodies for offers protocols for affinity maturation and reducing immunogenicity of antibodies. Discusses the novel applications of antigen-binding affinity and specificity. DNLM: Antibodies--therapeutic use--Laboratory... |
 | Therapeutic Antibodies: Methods and Protocols (Methods in Molecular Biology) With revenues from the top five therapeutic antibodies accounting for a majority of the recent pharmaceutical sales, the research and development in the field has exploded over the past several years and is expected to grow with new emerging monoclonal antibodies like Numax, Lucentis, Actemra, and others. In Therapeutic Antibodies: Methods and Protocols, leading experts from academic laboratories... |
 | Making and Using Antibodies: A Practical Handbook Antibodies are an indispensable tool in the study of biology and medicine. Making and Using Antibodies: A Practical Handbook presents techniques in a single, comprehensive source for the production and use of antibodies. It enables researchers to immediately access lab-tested, proven protocols. Written and edited by an elite team of scientists, who have developed and refined many of the... |
 | Basic Methods in Antibody Production and Characterization Written for researchers and professionals in the fields of biomedical research, immunology, biochemistry, molecular biology, pathology, and biotechnology, Basic Methods in Antibody Production and Characterization uses a cookbook approach to presenting the methods for the production, characterization, and use of antibodies. Antibodies described include polyclonal and monoclonal and those made by... |
 | Handbook of Therapeutic Antibodies 3-Volume Set In this most comprehensive reference source for the development, production and therapeutic application of antibodies, Volume I contains general chapters presenting established technologies and clinical applications. Volume II provides a look at emerging technologies, new therapeutic concepts, and clinical studies. The third volume features detailed and specific information about each currently... |
 | Monoclonal Antibodies: Methods and Protocols (Methods in Molecular Biology) Monoclonal Antibodies: Methods and Protocols examines a collection of state-of-the-art methods that employ monoclonal antibodies in a clinical setting with opening chapters focusing on the gold standard method for generating mouse monoclonal antibodies through hybridoma technology, future methods for engineering recombinant and humanized antibodies, methods for engineering soluble Fc fusion... |
 | Using Antibodies : A Laboratory Manual : Portable Protocol NO. I by Ed Harlow, David Lane Few technical manuals have become standards in biomedicine. Antibodies: A Laboratory Manual, by Ed Harlow and David Lane, has had that status for a decade. Now there is a new and even higher standard—Using Antibodies: A Laboratory Manual. Harlow and Lane have completely revised their guide to the use of immunoglobulin reagents in the laboratory. Chapters have been entirely rewritten,... |
 | Methods in Enzymology, Volume 92: Immunochemical Techniques, Part E: Monoclonal Antibodies and General Immunoassay Methods FROM THE PREFACE: Several papers in this volume deal with advances in hybridoma technology and complement the chapter by Galfri and Milstein that appeared in Volume 73 of this series. Methods to enhance the efficiency of producing desired fusion products, to simplify the basic procedures involved, and to assess the specificity and other properties of monoclonal antibodies are discussed.... |
 | Recombinant Antibodies for Cancer Therapy: Reviews and Protocols (Methods in Molecular Biology) (Methods in Molecular Biology) Axaron Bioscience AG Heidelberg, Germany. Presents a survey of the current status of engineered antibodies and describes in detail many readily reproducible methods of generating the novel and promising antibody-based reagents of today's cancer therapy. DNLM: Antibodies--therapeutic... |
| © 2008 BrightSurf.com |