September 26, 2012
(International Herald Tribune) -- Personalized animal models are being used to determine the best treatment for a patient. Some researchers call them avatars, like the virtual characters in movies and online games.
Dr. Megan Sykes, a medical researcher, has a mouse with a human immune system -- her own. She calls it "Mini-Me."
There are also mice containing a part of 9-year-old Michael Feeney -- a cancerous tumor extracted from his lungs. Researchers have tested various drugs on the mice, hoping to find the treatment that would work best for Michael.
In what could be the ultimate in personalized medicine, animals bearing your disease, or part of your anatomy, can serve as your personal guinea pig, so to speak. Some researchers call them avatars, like the virtual characters in movies and online games.
"The mice allow you the opportunity to test drugs to find out which ones will be efficacious without exposing the patient to toxicity," said Colin Collins, a professor at the University of British Columbia.
Experiments on mice have been done for decades, including implanting people's tumors into the animals. But the techniques have improved in the past few years and interest is growing. The National Institutes of Health in Bethesda, Maryland, held a workshop on personalized animal models this month. And while the models are mainly being used for research, companies are beginning to commercialize them for use in drug development and medical treatment as well.
Experts caution that it has not been proved that the use of avatars will prolong the lives of cancer patients. And it costs tens of thousands of dollars, which insurers will not cover, to create and test a colony of the animals.
"It's an act of faith to say this is a superior way of proceeding," said Dr. Edward Sausville, a professor of medicine at the University of Maryland.
But some cancer patients, wanting to try everything possible, are turning to the mice anyway.
"This just seems right to us," said Jill Feeney, the mother of Michael, who has been fighting a type of bone cancer called Ewing's sarcoma since 2009, when he was 6. "It's actually his tumor growing somewhere, and we're treating it the way he would be treated."
When Michael had surgery in February to remove a tumor that had spread to a lung, a courier was waiting outside the operating room in New York to whisk the tumor to a laboratory in Baltimore run by a company called Champions Oncology.
Four hours later, technicians cut the tumor into five pieces and placed each piece under the skin of an anesthetized mouse. Two months later, after the tumors had grown, they were removed, cut into pieces and each piece implanted in another mouse. A month later there were enough mice models to begin testing.
The Feeneys, who live in Ridgewood, New Jersey, paid $25,500 for the creation of the avatars and for the testing of four different drugs or drug combinations.
The results came back in July. A combination of four drugs -- gemcitabine, docetaxel, Avastin and Afinitor -- was "astonishingly active" in shrinking the tumor in the mice, said Michael's oncologist, Dr. Leonard H. Wexler of the Memorial Sloan-Kettering Cancer Center in New York. Dr. Wexler said that the combination had not been something oncologists would typically choose.
Michael has not tried the combination yet because he is participating in a clinical trial of an experimental drug. But if that drug does not work, his mother said, "we have the home run in the back pocket."
Cancer is not the only area where the animal models may be useful.
Dr. Sykes, a professor at Columbia University in New York, led the team there and at Massachusetts General Hospital that replicated an individual's immune system in mice using a bone marrow sample from the person's hip.
The immediate goal is to study how Type 1 diabetes, an autoimmune disease, develops. But in the future, she said, such "personalized immune mice" might produce immune cells that could be transplanted into the patient to help fight disease.
At Washington University in St. Louis, Dr. Jeffrey I. Gordon has transplanted the collection of bacteria in a person's intestines into mice. The "humanized" mice might be used to study, for instance, how a change in diet could influence the person's health.
In cancer, drugs that work in mice do not always work in people. But some studies suggest that tumors freshly implanted from patients more closely resemble human disease than those created by the common technique of implanting tumor cells that have been cultured in a laboratory dish.
"It's the closest we can get to the real deal," said Alana Welm, a breast cancer researcher at the University of Utah.
At the Mayo Clinic in Minnesota, avatars are being used to "immortalize" tumors from patients in a clinical trial. The Jackson Laboratory in Sacramento, California, is building a big collection of personalized animal models representing various cancer types to use in studies.
Companies like Oncotest, based in Germany, and StemMed in Houston are helping pharmaceutical companies do clinical trials on the mouse surrogates of patients.
Researchers at Bayer Schering Pharma, for instance, tested an experimental drug on mice stand-ins for 22 people with lung cancer. By comparing the 14 mice for which the drug worked with the 8 for which it didn't, they figured out how to improve the drug's effectiveness, according to a paper in Clinical Cancer Research.
Still, the stand-ins are not perfect surrogates. A tumor implanted under the skin of a mouse might not behave the same as it did in the human breast, lung or other organ from which it was extracted. Unlike people, the mice are bred to have deficient immune systems, so they will not reject the human tumors.
There are also practical problems. Sometimes, patients' tumors do not grow in the mice at all, and it takes at least four months to create enough mice to test a reasonable number of drugs.
Dr. Harvey Pass, a thoracic surgeon at New York University, said four of the eight patients he had referred to Champions had died before any results from the mice had come back.
Dr. Ronnie Morris, the president of Champions, said that the company had had about 160 patients so far and had tested drugs on mice for 60 of them.
The other patients either had died too soon, or the tumors had not grown in the mice, or the patients had been too new to have reached the drug testing stage.
Champions, started by two prominent oncologists from Johns Hopkins University in Baltimore, published a paper last year reporting on 14 patients. The mouse testing found a drug or drug combination that could shrink tumors for 12 of them.
Tumor shrinkage does not always mean longer life, however, and skeptics say randomized trials are needed to prove patients using avatars will fare better than they would have otherwise. Better evidence is also likely to be needed before insurers will pay for the use of avatars.
In one room of Champions' lab recently, David Vasquez, a scientist, picked up an anesthetized mouse, made a small slit in its back with a knife, slipped a tiny piece of tumor from a nearby petri dish under the skin, then stitched the mouse up. The process took about five minutes.
Another room is full of cages of the nude mice, so-called because the genetic abnormality that makes them immunodeficient also leaves them hairless. Huge tumors bulge from the left sides of some of the mice.
But if a drug is working, the bulge is barely visible. The mice are killed if the tumor is removed for transplanting into more mice or is causing too much suffering.
Some experts say that testing a tumor for genetic mutations is a far more practical way to figure out which drug may work best. But that technique, at least for now, does not always yield a useful result.
Nir Toib, an Israeli filmmaker with lung cancer, said that treatments suggested by a genetic analysis of his tumor had not worked, but that a combination of two drugs suggested by the avatar testing had.
"I had 10 tumors on my right kidney," said Mr. Toib. "All of them disappeared."
While Mr. Toib joked that he had himself "cloned" in the mice, neither he nor most other patients feel any personal attachment to their mice.
"You just look at it as a tool for saving yourself," said a 60- year-old man from New Jersey with lung cancer, who had asked that his name not be used to protect his privacy. "From my perspective, the more that die, the better for me."
Ms. Feeney said that she had bad memories of the mice that infested her first apartment in New York. And she said Michael "was a little upset to hear we would be giving mice cancer and that we might kill them."
But if Michael is saved by a treatment resulting from testing on his avatars, she said, "I will love these mice forever."
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