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Jackson Lab trial to test Hartford patients’ tumors in mice

  • by Arielle Levin Becker
  • April 30, 2013
  • View as "Clean Read" "Exit Clean Read"

The Jackson Laboratory will team up with Connecticut Children’s Medical Center and Hartford Hospital for a clinical trial of “cancer avatars,” growing tumors from human patients in mice as a way to determine the best therapies for each patient’s disease.

Hartford Hospital President and CEO Jeffrey A. Flaks offered a glimpse at one of the goals of the work: “We’re going to have patients who come to us, and we’ll be able to treat them in a way that says, ‘For you, for your particular tumor, for your cancer diagnosis, we can perfect with extraordinary precision the exact medications, the exact treatment regimens that provide you with the best care possible.'”

Gov. Dannel P. Malloy joined Jackson Lab and hospital leaders to announce the trial Tuesday, touting it as evidence that the state’s massive investment in bioscience — including nearly $300 million to help Maine-based Jackson build a new institute at the UConn Health Center in Farmington — was paying off.

The trial will be small at first, testing the capabilities of a new approach, and will be focused on patients with a high risk of recurrence. Dr. Edison Liu, Jackson’s president and CEO, cautioned that although he and others have hope for the concept, he didn’t want to overhype the idea.

“There’s going to be a lot of hard work,” Liu said.

Here’s how it will work: Once a patient is identified as meeting the trial’s criteria and agrees to participate, his or her tumor will be extracted and split.

Part of the tumor will go to Jackson’s Connecticut institute, where researchers will analyze it.

Another part will go to a Jackson facility in California, where scientists will attempt to grow it in a specially engineered type of mouse with a suppressed immune system, allowing the foreign tumor to take hold.

Once the tumor grows in the mice — it can take four months to a year — researchers can try different treatments to see which are effective in combating the patient’s tumor.

And a team of clinicians, pathologists, scientists and computer analysts at the two hospitals in Hartford will review all the information generated to determine what it means for treating the patient.

Liu said he jokingly refers to the work as rocket science. Sending a man to the moon didn’t break new conceptual ground, he said, but represented a massive coordination of technologies and infrastructure. “It’s the same thing here. Perhaps not as grand, but still it’s the same principle,” he said.

The Jackson Laboratory for Genomic Medicine, the lab’s Connecticut institute, is aimed at making advances in “personalized medicine,” and the cancer avatar concept, if it works, is one form of it. The idea is to better tailor treatments to a person’s particular condition and characteristics.

Many of the tools now used in medical treatment are fairly blunt instruments. Chemotherapy, for example, works on some patients, but many who get it don’t improve, and others face severe side-effects. Researchers pursuing personalized medicine hope that by gaining a better understanding of the tumors they’re targeting, and of the genetic makeup of the person being treated, they’ll be able to more precisely target the therapies.

Dr. Fernando Ferrer, surgeon-in-chief and executive vice president at Connecticut Children’s, said Tuesday that a new approach to children’s cancer is sorely needed. After making tremendous advances in treating pediatric cancer in the late 20th Century, progress stalled, he said.

“We desperately need new approaches to treat children with cancers that fail the treatments we’ve designed thus far,” he said. “Our increasing ability to leverage our knowledge of the human genome provides us this way forward. It provides us a new strategy, so to speak, to tackle this problem.”

Researchers can already identify mutations and “gene signatures” in certain tumors, but they generally don’t yet know what to do with that information, limiting its ability to produce precise treatments, said Dr. Andrew Salner, director of Hartford Hospital’s Helen and Harry Gray Cancer Center. For most mutations, it’s not clear how important they are in the tumor cells’ survival, and there aren’t drugs to target the mutations, Salner said.

The “cancer avatar” approach will help build on what researchers can find out about a tumor’s makeup by allowing them to see how the tumor responds to certain therapies and how it behaves in mice, Salner said.

“Those two bits of information together, there’s some synergy there because it allows us to develop a much more personalized approach to the patient,” he said.

Salner said the work will be helpful for patients who are at high risk of problems after their initial treatment. “We need to know what therapies we can offer them next after the initial up-front treatment, for example, the removal of their tumor or radiation afterwards, that will offer them a likelihood and prospect of long-term survival,” he said.

The clinical trial is expected to include certain types of pediatric cancer and colon cancer in adults. Liu said it’s not yet clear when the first tumors will be gathered, but he said the goal is for recruitment to begin right away.

The three institutions participating are funding the trial internally, and there will be no cost to patients, Liu said.

The trial will build on work Jackson Laboratory has been doing for several years. Four years ago, Jackson started an effort to develop a “library” of human tumors, getting donated samples from patients through affiliated institutions, including University of California Davis, the Scripps Research Institute in California, and Swedish Hospital in Seattle. There are now 22 institutions in the consortium.

Jackson, which originated as an institute to study cancer in mice, developed the mice that will be used in the trial. They’re known as NSG mice and have suppressed immune systems.

Liu said Jackson is talking with other hospitals, both in Connecticut and nationally, about potentially joining the trial.

Malloy, who has put millions of state dollars toward trying to establish the state as a center for bioscience research, said the trial shows that Connecticut’s commitment is paying off.

“In a relatively short period of time, we are seeing what we said would happen, actually happen,” he said.

Malloy called it “an exciting announcement about the future of medicine, not just in Connecticut, but in the world.”

Liu called the announcement “the first step of a long journey ahead,” “the first installment of the Jackson Lab’s promise that we will make you proud.”

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