Abgenix in the news too
mercurycenter.com
Human genes turn mice into
`pharm animals'
BY LISA M. KRIEGER
Mercury News
Forget building a better mousetrap. For $45 million, Abgenix Inc. has figured out a
way to build a better mouse.
It looks like your usual rodent on the outside, with a sleek coat, beady eyes and long
tail.
But inside, it is quite extraordinary. That's because it's not all mouse -- it's part
person, carrying genes plucked from human cells.
While it still prefers cheese to chess or crossword puzzles, the mouse's implanted
human genes can crank out vast numbers of custom-made human ``monoclonal
antibodies'' -- potentially valuable weapons in the war against mankind's most deadly
diseases, ranging from cancer to heart disease.
Of mice and men, these chimeric creatures become, in essence, tiny pharmaceutical
factories. If as prolific and therapeutic as hoped, the Abgenix mouse could pay off, big time, for the small Fremont-based
biotech company.
An estimated 7,000 to 9,000 of these ``pharm animals'' are bred and fed in Abgenix's climate-controlled facilities, then
shipped off in ventilated FedEx boxes to labs around the world. Thousands more are grown in the labs of the company's
competitor, Medarex Inc. of Annandale, N.J.
``Our hope is that this mouse will become a universal tool of medicine, helping as many people as possible,'' said Kate
Maynard, director of operations for Abgenix.
The rodents create optimism in a field that, even in the usual turbulence of biotech, has hit more than the usual number of air
pockets.
The first generation of monoclonal antibodies, highly hyped in the mid-'70s, failed to win approval by the U.S. Federal Drug
Administration. Built before scientists knew how to splice human genes into animals, these mouse-generated ``magic bullets''
were busts, ineffective and rejected by the body.
Things improved with the creation of hybrid antibodies, constructed using genetically engineered human/rodent combinations
of gene fragments. Hybridized DNA created antibodies that looked more familiar to the human body.
But the pure-human antibodies produced by the Abgenix and Medarex mice promise an even better outcome.
The goal is for these Y-shaped proteins, when injected into sick people, to hunt down and disable diseased cells. Because the
human body does not perceive these antibodies as mouse-like, it does not develop an immunity to them.
The technique is this: First, scientists isolate from human cells some of the DNA that encodes for parts of our immune system.
This human DNA is injected into three-day-old mouse embryos, smaller than a grain of sand. Then, using a pipette, lab techs
blow the embryos through an incision to a mother mouse's oviduct, taking care not to inhale.
When the mom mouse gives birth, an average of one-half of her offspring are ``transgenic.''
The real moment of truth comes when these transgenic mice are confronted by an antigen, such as an injected virus or cancer
cell. With luck, the rodents start spewing out protective antibodies -- human antibodies.
These antibodies are harvested from the animals' blood or lymph and analyzed. Then they are fused with a special cell line, so
that massive volumes of antibodies can be churned out. If the Abgenix approach works, someday thousands of liters of the
substance may be needed to meet patient demand.
Living in a sterile lab -- tended by techs wearing surgical masks, gowns and gloves -- the animals are exposed only to specific
antigens in an effort to trigger only specific antibodies.
The ultimate goal is to create a wide repertoire of antibodies, each potent against a different invader. Abgenix is working on
three of its own ``antibody targets'' as well as 30 other projects for major pharmaceutical and biotech companies.
``These are special animals,'' said Maynard. ``These animals are our whole company's business.'' |
