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By David Templeton, Pittsburgh Post-Gazette

PITTSBURGH — With no more treatments available, the Oxford, Connecticut, man undertook the dreaded task of discussing with his wife how his demise would affect her, their 5-year-old son and 1-year-old twins.

Rounds of chemotherapy, drug treatments and a bone-marrow transplant all had failed to put Paolo Cavalli’s adult B-cell acute lymphoblastic leukemia into remission. His prognosis was poor.

“With no treatment, I was looking at that time frame” of a few months, he said.

But in a happy twist of fate, Cavalli would receive a new cancer treatment called cancer immunotherapy, which uses the immune system to fight cancer. It’s a field many researchers now are pursuing, with University of Pittsburgh immunologist Olivera Finn being one of its pioneers.

In a phase one human clinical trial, a Memorial Sloan Kettering Cancer Center team in New York City used a gene to engineer patients’ immune cells to attack B-cell leukemia. The results were dramatic. Of 16 patients suffering the final stages of B-cell leukemia, 14 went into complete remission, including Cavalli.

The study, published online Wednesday in Science Translational Medicine, says “the results strongly support the therapeutic potential” for engineered immune-cell therapy.

“These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies,” stated Michel Sadelain, director of the Center for Cell Engineering at the cancer center. “Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”

Sloan Kettering’s success with the blood-based cancer raises optimism that the method could be adapted to target tumor-based cancers, including lung, pancreatic, breast and prostate.

T cells are immune cells that attack viruses, bacteria and parasites. In Sadelain’s therapy, T cells taken from the patient are engineered in the laboratory to include a gene that makes the T cell target the CD19 protein on the surface of B cells, including cancerous ones.

When the T cells are reintroduced into the patient, they target cancerous B cells, leading to remission in as few as eight days but more typically within 24 days. Sadelain said he has some understanding of why two patients didn’t respond to the treatment.

The “living cell” treatment involves T cells replicating themselves inside the body to pose a persistent threat to cancer cells, eventually leading to remission. “In the treatment, we remarkably induced complete remission with engineered T cells,” Sadelain said.

Next, Sadelain will conduct a phase two trial with more patients to confirm results, with the goal of persuading the U.S. Food and Drug Administration to forgo requirements for a phase three trial, which can be cost-prohibitive. Finn said that’s also her hope with her vaccine for colorectal and other tumor-based cancers.

Traditional therapy for the B-cell leukemia involves rounds of chemotherapy and drug treatments in pursuit of complete remission, which allows a person to undergo a bone-marrow transplant. In that procedure, the cancerous bone marrow is destroyed and replaced with healthy bone marrow from a donor.

Because it’s still unclear whether the treatment can be curative, 10 of the patients in remission underwent bone-marrow transplants, with two deaths resulting from transplant complications, Sadelain said.

Finn, a distinguished professor of immunology in Pitt’s School of Medicine, is engineering immune cells to target and destroy an abnormal variant of protein that exists on the surface of precancerous and cancer cells. That protein is necessary for the cancer to survive and progress.

The immune response engineered by the vaccine destroys precancerous cells on polyps in the colon and prevents development of colon cancer in those predisposed to the disease. She’s also testing the vaccine in pancreatic, lung and breast cancers that feature the same abnormal protein.

Finn wasn’t involved in the Sloan Kettering study, but she said she’s familiar with it. The success was expected.

“I think Michel (Sadelain) is one of the best” in that approach to treating cancer, she said. “The results, as good as they are, occurred because he is dealing with a blood cancer that is more susceptible to T cells. Now we are waiting to see how they work in pancreatic, lung and breast cancer, which are tumor cancers.”

Even with expected results, the high success rate “is wonderful,” she said.

“In that particular disease and that target, it would have been expected, and it’s nice that they got those results,” said Finn, whom Sadelain described as a luminary in the growing research field of engineering immune cells against cancer.

Cavalli, who operates three Cavalli Pizza restaurants, said he’s optimistic about his health but is living day to day. He’s feeling well, he said, eight months after the June treatment. But in a risky decision, he will not undergo bone-marrow transplant, with expectations the treatment cured his leukemia, thanks to Sadelain and team.

“All the doctors that I’ve seen are brilliant,” Cavalli said. “We need more people like them. Dr. Sadelain not only is an intellect but he’s also a great person. He’s positive and he’s optimistic. He’s the type of person that changes the world.”

Photo: epSos.de via Flickr

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