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Penn cancer treatment continues to move ahead

CAR therapy for cancer has moved into the fast lane. The University of Pennsylvania and Children's Hospital of Philadelphia on Thursday published the latest results of their novel "chimeric antigen receptor" - CAR - immune therapy. Of 25 children and five adults with end-stage leukemia, 90 percent saw their cancer disappear and 67 percent were cancer-free six months later. The longest remission has lasted almost three years.

The 30,000-square-foot Center for Advanced Cellular Therapeutics, funded in part by Novartis, will be built atop a new addition to the rear of Penn’s Perelman Center for Advanced Medicine. (Penn Medicine photo)
The 30,000-square-foot Center for Advanced Cellular Therapeutics, funded in part by Novartis, will be built atop a new addition to the rear of Penn’s Perelman Center for Advanced Medicine. (Penn Medicine photo)Read more

CAR therapy for cancer has moved into the fast lane.

The University of Pennsylvania and Children's Hospital of Philadelphia on Thursday published the latest results of their novel "chimeric antigen receptor" - CAR - immune therapy. Of 25 children and five adults with end-stage leukemia, 90 percent saw their cancer disappear and 67 percent were cancer-free six months later. The longest remission has lasted almost three years.

The Food and Drug Administration in July gave the CAR therapy "breakthrough" designation, intended to expedite its approval. Testing in children with leukemia is expanding to nine other pediatric centers, while Penn has added CAR trials in Non-Hodgkin's lymphoma and soon, glioblastoma, the fearsome brain cancer.

Last month, Penn and commercial partner Novartis unveiled plans for a 30,000-square-foot facility that will open in 2016 on the university's West Philadelphia campus. It will double Penn's capacity to take patients' own immune cells and reprogram them using CAR technology to hunt down cancer cells.

And that will give more terminally ill children a chance to become like 11-year-old Tori Lee: normal. The Ocean Township, N.J., girl got the CAR therapy 18 months ago, after years of toxic chemotherapy failed to cure her.

"She does all the normal kid things - complains about homework and doesn't want to go to school," said her father Chris Lee. "It's music to our ears."

Penn gene therapy pioneer Carl H. June, who has led the CAR research team, said, "The past five years have been a time of explosive, exciting progress in the field of cancer cellular therapy."

With many of the "brave" initial leukemia patients now thriving, "we hope to offer that chance to patients with many other types of cancer," he said.

For all the excitement, the progress has not come without sadness and setbacks.

The updated results - which are in the New England Journal of Medicine and build on data presented by the researchers in December - include seven patients who had their acute lymphoblastic leukemia eradicated, only to relapse from six weeks and 8.5 months later.

Two of them - Maddie Major, 9, of La Platte, MD., and Logan Parker, 8, of Ocean Township, N.J. ( he goes to school with Tori Lee) - are each preparing for bone marrow transplants. Their second transplants.

The harrowing procedure will put Maddie "at risk for so many complications I can't write or bear to think of them all," her mother, Robyn Major, wrote last week on Facebook.

Penn and Novartis are also fighting a CAR patent infringement lawsuit brought in 2012 by St. Jude Children's Research Hospital in Memphis. St. Jude's commercial partner, Juno Therapeutics Inc. of Seattle, joined the fight this year.

In an e-mail, a Novartis spokesperson said the company maintains that Juno's patent and its lawsuit are invalid. "We are confident that our position will be upheld in court," the e-mail said.

The lawsuit is just one sign of the red-hot race to add CAR therapies to the oncology arsenal. Dozens of trials of CAR therapies are now underway, including some in Europe.

A CAR is basically a genetically engineered marker protein that can be grafted onto an immune system soldier called a T cell. The CAR activates the T cell to attack any cells bearing the same marker.

The approach has posed huge obstacles. Cancer arises from the body's own cells, so T cells are profoundly tolerant of these renegades. By the same token, overriding this tolerance with a marker protein is risky, because markers found on cancer cells are also usually on healthy cells.

That's why most of the success to date with CAR therapies has been reported in blood cancers in which B cells turn malignant. B cells, which normally help fight infection, have a unique protein marker not found on any other cells. B cells are not indispensible to the body, so the patient can afford to lose both healthy and malignant B cells to the CAR-driven T cells.

That's not to minimize the temporary side effects. All of the patients treated at Penn and Children's suffered serious - and in several cases, catastrophic - reactions when the CAR T cells went into overdrive.

However, researchers have used a new rheumatoid arthritis drug, Actemra, to counter the worst effects, and no patients have suffered permanent damage from the therapy.

The latest study is not the first to report high remission rates in B cell blood cancers, said Children's Hospital oncologist Stephan Grupp, one of the authors.

"But where our data differ, in addition to having a 90 percent response rate, two-thirds of the patients remain in remission six months afterward, with no further therapy," Grupp said.

The researchers speculate that their CAR T cells are better at multiplying and persisting in patients' bodies.

Enrollment has continued since the published data were compiled. Through this month, a total of 40 children and 15 adults with acute lymphoblastic leukemia (ALL) have been treated, said Penn oncologist David Porter.

"This represents a really powerful therapy for ALL," Porter said. "We've treated enough patients to confirm that. It's time to start multi-center trials."

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