Research finds headway in fighting late ovarian cancer

Posted: April 08, 2013

University of Pennsylvania researchers believe they are making headway in boosting the immune system to fight a formidable foe - late-stage ovarian cancer.

On Saturday, the scientists presented results from the first 31 patients to receive experimental immune therapies made from their own cells, plus anticancer drugs.

Distinguishing the effects of the novel therapies from conventional drugs is tricky, especially since two women who have remained cancer-free were in remission when they joined the study.

But the researchers say the signs are encouraging: Twenty-one women whose tumors shrank or did not progress for extended periods had evidence of strong immune cell activation from the personalized therapies. The eight women who saw no benefit did not have the immune reaction.

"It's not a slam dunk," said Penn's Lana E. Kandalaft, a presenter at the American Association of Cancer Research meeting. "But the more we do, the more we learn."

Penn is at the forefront of the emerging field of cancer immunotherapy - manipulating the patient's individual immune system to terminate, rather than tolerate, malignant cells. The immune system doesn't automatically perceive cancer as a threat because it arises from healthy native cells.

Over the last two years, Penn researchers led by gene-therapy pioneer Carl June have had stunning early success with a leukemia immunotherapy made from patients' disease-fighting "T cells." It has eradicated several types of advanced, intractable leukemia and kept them away for as long as 30 months in a small but growing number of children and adults.

Now, June's technology is being adapted to treat solid-tumor malignancies such as ovarian cancer.

This is a much tougher challenge. The leukemia therapy works by homing in on a marker, or "antigen," on B cells, the blood component that turns rogue in the disease. But ovarian tumors have no easy target. In fact, many ovarian cancer antigens haven't yet been identified.

The experimental ovarian cancer treatment has evolved to include more and more avenues of attack, Kandalaft said.

The core of the attack is a vaccine made from the patient's "dendritic cells." The job of these cells is to gather unfamiliar antigens and present them to disease-fighting T cells. In this case, the dendritic cells are primed in the lab by being exposed to an antigen-laden, liquefied sample of the patient's tumor.

The patient also gets chemotherapy to  deactivate certain cancer-tolerant immune cells, and a cancer drug, Avastin, that inhibits the growth of nourishing blood vessels around the tumor.

If the patient doesn't respond, or runs out of vaccine doses, or both, she can then have a second course of immunotherapy. It is made by removing the antigen-primed T cells from her blood, multiplying them, then reinfusing them to attack her cancer. Of the 11 patients who had this second-phase therapy, seven had their cancer shrink or stop progressing, and one temporarily became cancer-free.

The two women who remain in extended remissions had the dendritic cell vaccine, but not the T cell immunotherapy. Before the study, both had reached the point where they needed continuous chemotherapy to keep their ovarian cancer from returning.

"I've had almost four years of remission, with no chemotherapy - not anything," said Elizabeth Thomasson, 51, of Severna Park, Md. "That break has given me renewed strength. If it comes back, I could fight again. But I love my life right now.

"My first grandchild was born the day after my diagnosis. Now she's 5, and my sixth grandchild is going to be born in two weeks. I thought I'd never get time with any of them."

Before joining the study, Philadelphia dentist Yi Zuo, 50, suffered chemo-related fevers, bone damage, fatigue, thinking problems, nausea, and something that threatened her career - finger numbness.

"It's been almost a year and a half" since she stopped chemo, she said. "All my scans and tests since that time have showed no sign of cancer. Hopefully, this opens a new process for treating cancer."


Contact Marie McCullough at 215-854-2720 or mmccullough@phillynews.com.

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