Anti-cancer antibodies produced in chickens

Aug 29 2005

A team of researchers have produced the first fully functional, human sequence monoclonal antibodies (mAbs) in chickens.

The antibodies were in the chicken oviduct and deposited into egg white in concentrations of 1-3 milligrams per egg.

These antibodies apparently possess a far greater cell-killing ability compared to therapeutic antibodies produced by conventional cell culture methods.

The researchers from Origen Therapeutics and Medarex, Texas A&M University and the University of California, Los Angeles, believe their 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.

Robert J. Etches, Origen Therapeutics vice president, says that the antibodies produced by this method have very similar physical and biological characteristics to those produced in CHO cells.

In order 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.

The final cell combo with large contributions from the stem cells lay eggs, contains milligram amounts of antibody, which is then separated from the egg white proteins, creating the purified product.

Dr. Etches believes the work represents considerable progress in the development of avian transgenes.

He explains that monoclonal antibodies have been very successful as human therapeutics, with over 17 approved for human therapeutic use.

He expects 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.

He says 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.

Robert Kay, Ph.D., Origen Therapeutics president and chief executive officer says they believe the chicken system is an attractive one for therapeutic protein production compared to either plant systems or to other transgenic animal systems.

According to Kay because the chicken-produced anti-cancer antibodies show dramatically enhanced cell killing activity, in relation to other non-traditional production technologies and some traditional cell culture methods, the system is superior.

He says that unlike other transgenic animal systems, the time from antibody identification to production in eggs can be as short as 8 months compared to up to 3 years for goats or cattle.

Furthermore the egg is sterile and stable, and provides good initial material for isolation and purification of the protein.

Also conditions for good manufacturing practices are well established for vaccine production in chicken eggs.

According to Matthew E. Portnoy, Ph.D., program director at the National Institute of General Medical Sciences at the National Institutes of Health, the new technology has the potential to drive down drug manufacturing costs, which could make medicines and health insurance plans less expensive.

Origen Therapeutics is a privately held biotechnology company in Burlingame, California, developing product opportunities from an emerging avian transgenic platform.

The company's mission is to become a leading developer and producer of complex recombinant protein therapeutics, including human polyclonal antibodies.

Attracted by the speed and economy with which transgenic chickens can be produced, Origen is working to establish corporate alliances with biotechnology and pharmaceutical companies for the commercialization of its products.

The new report, appears as an advance online publication for the September 7 issue of Nature Biotechnology.

A research brief commenting on the potential impact of this development for the production of human therapeutic proteins will also appear in the September issue of Nature Medicine.

The work conducted at Origen Therapeutics and Texas A&M University was supported by a National Institutes of Health Small Business Innovation Research Grant from the National Institute of General Medical Sciences. Research in the laboratory at UCLA was supported by grants from the National Institutes of Health.