Seeking Cures, Patients Enlist Mice Stand-Ins

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Seeking Cures, Patients Enlist Mice Stand-Ins

By ANDREW POLLACK

Published: September 25, 2012

BALTIMORE - Sykes, a medical researcher, has a mouse with a human immune

system - her own. She calls it " Mini-Me. "

Feeney, 9, who has Ewing's sarcoma, at home in New Jersey with his

mother, Jill.

There are also mice containing a part of 9-year-old 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 .

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 , 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 last few years

and interest is growing. The National Institutes of Health held a workshop on

personalized animal models earlier 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.

Sausville, a professor of medicine at the University of land.

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 , 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 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 here 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

into another mouse. A month later there were enough mice models to begin

testing.

The Feeneys, who live in Ridgewood, N.J., paid $25,500 for the creation of the

avatars and 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 's oncologist, Dr. Leonard H. Wexler of the

Memorial Sloan-Kettering Cancer Center. Dr. Wexler said that the combination was

not something oncologists would typically choose.

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, 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 can be

transplanted into the patient to help fight disease.

At Washington University in St. Louis, Dr. 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.

Keren Paz, a vice president at Champions, inspects mice with shrunken tumors.

" 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, avatars are being used to " immortalize " tumors from patients

in a clinical trial. The Laboratory in Sacramento 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 eight 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 a deficient immune system, so they will not reject the human tumor.

There are also practical problems. Sometimes, patient 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 referred to Champions died before

any results from the mice came back.

Dr. Ronnie , the president of Champions, said the company has had about

160 patients so far and has tested drugs on mice for 60 of them. The other

patients either died too soon, or the tumor did not grow in the mice, or the

patients are too new to have reached the drug testing stage.

Champions, started by two prominent oncologists from s Hopkins, 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 would pay for the use of avatars. In one room of Champions' lab

recently, 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 immune deficient 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 treatments suggested by a genetic analysis of

his tumor did not work, but that a combination of two drugs suggested by the

avatar testing did.

" 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 New

Jersey man with lung cancer who 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 Brooklyn.

And she said " was a little upset to hear we would be giving mice cancer

and that we might kill them. "

But if is saved by a treatment resulting from testing on his avatars,

she said, " I will love these mice forever. "