UM/Jackson Trial Fights Liver Cancer with Natural Killer Cells

15/12/2010 03:41:00

Encarnacion Miranda knew he didn’t have long to live when, in October 2009, he learned that his liver, deeply scarred by the hepatitis C virus he had contracted from a blood transfusion years before, had triggered hepatocellular carcinoma (HCC), the most common liver cancer.

But on Thursday, a day after walking six miles, and seven weeks after becoming the first person in the U.S. with HCC tumors to receive a transfusion of Natural Killer Cells extracted from a donated liver, Miranda appeared with a team from the Miller School and Jackson Memorial Hospital to extol the multi-pronged treatment that made him eligible for a liver transplant, and the promising new clinical trial that may help him, and eventually many of the four million Americans with hepatitis C at risk for developing HCC, stave off a recurrence of the deadly cancer.

“I feel like a completely new person,’’ Miranda said. “I don’t feel tired. I don’t feel anything. It is remarkable – the difference between how I felt then and how I feel now.’’

The Army veteran from Key Largo owes the difference to the multi-disciplinary team of transplant surgeons, hepatologists, oncologists and interventional radiologists who helped him qualify for the nation’s first clinical trial of the Natural Killer Cell (NK cell) immunotherapy developed at the University of Hiroshima in Japan as a potent weapon against HCC. A growing world epidemic, HCC is most commonly caused by hepatitis C in the U.S. and other western nations.

Liver transplants are now standard therapy for selected HCC patients, but members of the UM/Jackson team know too well that about 20 percent of transplant patients – 15 percent at the Miami Transplant Institute – with primary liver cancer end up dying from a recurrence of the cancer in the replacement liver. The reason, they believe, is that cancer cells remain in the bloodstream even when the tumors are removed or destroyed, or the diseased organ replaced.

So Andreas Tzakis, M.D., Ph.D., professor of surgery and director of the Institute’s Liver/GI Transplant Program, said the team was intrigued by the clinical trial in Japan led by Masahiro Ohira, M.D., Ph.D., that showed naturally occurring NK cells extracted from a healthy liver and enhanced to four times their potency in the lab act like smart bombs. When injected into the bloodstream, they hone in on and destroy any lingering cancer cells. They also have the added bonus of being 10 times more aggressive against the hepatitis C virus.

“You can call them a guided missile versus a smart bomb,’’ Tzakis said. “The important thing is they don’t kill any cells we don’t want them to kill. They kill just tumor cells.’’

In Hiroshima, 22 of 24 transplant patients who received NK cell transfusions after receiving partial livers from live donors remain cancer-free more than three years later.

The goal of the UM/Jackson trial, says David Levi, M.D., professor of clinical surgery and leader of the multidisciplinary team, is to enroll 25 patients and get the recurrence rate “down to zero.’’

Seigo Nishida, M.D., Ph.D., professor of clinical surgery and the trial’s principal investigator, brought the NK cell immunotherapy and Ohira to the Miller School, and secured the funding and FDA approval to begin the UM/Jackson trial. Unlike the Japanese trial, it is testing the cell-based therapy on patients who received livers from deceased donors.

“In Japan, we have few cases of cadaveric donor livers,’’ Ohira said. “So we have collaborated with each other in order to apply this study to cadaveric donor liver transplant in the U.S.’’

But before Miranda could volunteer for the experimental protocol, he had to qualify for a transplant, which he didn’t when the Miami Veteran Affairs Medical Center referred him to the Miller School in October 2009. He had too many tumors in his diseased liver, and they were too advanced.

That’s when the multi-disciplinary team began pulling out other relatively new weapons in their arsenal. Monitored by medical oncologist Jolly Varki, M.D., Miranda underwent specialized chemotherapy in which a catheter was threaded directly into the blood vessel feeding the cancerous liver. But that didn’t work.

So, Govindarajan Narayanan, M.D., chief of interventional radiology, tried burning the tumor with radiofrequency ablation. Inserting a probe heated by radiofrequency electrical current into the tumor, he essentially cooked it.

The next day, he added transarterial chemo embolization to the weaponry. Much like standard chemotherapy, the drug is threaded through the blood vessel. Only this time, the chemo is encapsulated in tiny beads that attack the tumors, a technique that allows the drug to diffuse more slowly, remaining at the tumors a longer period of time.

The tumors soon shrank and Miranda was eligible for the transplant list.

When a donor organ became available, surgeons collected NK cells from the liver, which Ohira enhanced in the lab, and just three days after Miranda’s October 19 transplant, millions of the stimulated NK cells were painlessly injected into his bloodstream.

“Two or three days after the surgery I was already walking and yesterday I walked six miles,’’ Miranda said Thursday. “I have no regrets and I can honestly tell you that today I feel great.’’

As Levi notes, Miranda’s case proves the value of the multi-disciplinary approach, and underscores the need for the kind of tailor-made treatments offered at UM/Jackson.

“There is no one good treatment for this cancer,’’ Levi said. “It’s really the right combination for the right patient that allowed us to achieve the results we are seeing. And it is our hope that the exciting early results of the NK cells will translate into real results in the lowering of the recurrence rate, making what we do from a multi-disciplinary approach even better.’’

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