Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First production of human monoclonal antibodies in chicken eggs published in Nature Biotechnology

29.08.2005


Chicken-produced antibodies demonstrate enhanced cell killing compared to conventionally produced anti-cancer antibodies

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."

Ellen M. Martin | EurekAlert!
Further information:
http://www.origentherapeutics.com
http://www.pacbell.net

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>