Magee-Womens Research Institute & Foundation

From a tiny, often undetectable starting point, ovarian cancer spreads quietly throughout a woman’s abdominal cavity, a deadly snow globe leaving seeds of disease that can regrow even after chemotherapy kills the initial lesions.

Worse, immunotherapy – which often boosts survival rates in other forms of cancer – has long failed to produce the same effect in ovarian cancer patients, frustrating doctors who are fighting to extend lives.

But clinical trials at Magee-Womens Research Institute hope to change those odds by rethinking the way chemotherapy impacts the immune system’s response. And, ironically, those trials were made possible by a gift that mimics the snow-globe effect: sowing seeds for larger grants from both the National Institutes of Health and the pharmaceutical industry to create a more lasting impact.

About 70 percent of ovarian cancer patients experience a recurrence, according to the Ovarian Cancer Research Alliance. Those rates fluctuate depending on the stage in which the disease is discovered; at stage 1, patients have about a 10 percent recurrence rate, while at stage 4, the rate is 90 to 95 percent. Most women are diagnosed in stage 3 or 4, because symptoms are often too subtle in earlier stages.

Until about 10 to 15 years ago, immune stimulants – designed to boost the body’s natural ability to fight disease – were thought to be ineffective against ovarian cancer during chemotherapy treatment, because doctors believed chemotherapy would kill the cells needed to stimulate the immune response.

The Magee trials work on the theory that chemotherapy may actually serve as an immune stimulant on its own. Similar studies have shown promise in colorectal and lung cancer, according to Dr. Robert Edwards, chair of Magee’s Department of Obstetrics, Gynecology and Reproductive Sciences and an investigator with Magee-Womens Research Institute who specializes in gynecologic cancer.

Starting about 10 years ago, Dr. Edwards and Dr. Anda Vlad, director of MWRI’s Cell Cytometry and Sorting core, began researching the synergistic potential of chemotherapy and immunotherapy on ovarian cancer. They began adding a series of immunotherapy cocktails to augment chemotherapy to see if they could mine immune responses out of tumors dying from chemo.

“No one ever looks at what happens in the tumor sites when you give chemotherapy, what the inflammatory response is from that,” explains Dr. Edwards.

As a dying tumor cell falls apart, it releases antigens, which can help with the immune response if doctors administer the right cocktail, they believe. If doctors could successfully introduce immunotherapy, they might extend the patient’s life.

To explore the theory, Dr. Vlad tested the combination regiment in animals with ovarian cancer that were more resistant to therapy, just like some women are. Mirna Bulatovic, a postdoctoral student, and clinical fellow Shannon Grabosch showed that cisplatin, the chemotherapy drug they were using, did not in fact wipe out the cells necessary for the immune system, opening a window in which an immunologist could intervene and stimulate the immune system to respond to tumors, preventing them from coming back.

“They had one main goal: to generate the data that would support the clinical trial,” says Vlad.

While the NIH wants projects that lead to new discoveries, attracting funds for the bridging effort that creates clinical trial-supporting data is difficult, Dr. Vlad explains.

To fill the gap, they used a $225,000 gift from Matt Deitch, whose mother, Robbie Lacritz Deitch, lost her battle with ovarian cancer in 2006. In her memory, Deitch – now a finance professional – donates to causes she championed.

That initial gift wound up paying extraordinary dividends. Using the data generated by Bulatovic and Grabosch, Drs. Edwards and Vlad wrote a proposal for a clinical trial that secured $1 million in funding from Merck. This ongoing trial allowed them to study the biology of the disease and how the combination of drugs and the way they are administered can extend patients’ lives.

Moreover, the therapeutic approach in the Merck trial was linked to another series of studies that Drs. Vlad and Edwards are leading in collaboration with Roswell Park Cancer Institute. Those efforts attracted another $1 million in funding from the NIH for a more expansive study, including a clinical trial in Pittsburgh. So Deitch’s initial gift generated approximately $2 million for ovarian cancer research; a second gift of $250,000 generated an additional $2.2 million for research by Dr. Vlad in conjunction with MWRI’s Dr. Ronald Buckanovich. Both were important to Deitch, who is interested in driving the maximum amount of impact through his donations.

“I’m sure it was the data that sold them,” says Dr. Edwards of Merck. “What we’re trying to do is actually promote long term survival, which is what immunotherapy can do that chemotherapy alone can’t do.”

Of 100 women with ovarian cancer, 85 may go into remission, he says. But within two years, the cancer will return in half of them. Within four years, that number rises to 70 percent, and within five years, half will die. In seven years, 90 percent die. Among those who lasted past the seven-year point was Darcel Fahy, who was a patient of Dr. Edwards and participated in his clinical trials prior to her death in 2017, including one which served as the precursor to the work performed by Bulatovic and Grabosch.

Darcel’s husband, Mike Fahy, credits the care she received from Dr. Edwards with extending his late wife’s life. Until the week she died, she fought for inclusion in research, believing that she could contribute to answers that might one day help someone else survive.

That is still Dr. Edwards’ goal: “It’s a very tough disease to address immunologically,” he says. “Our strategy is to attack multiple components of the immune system to try and change these numbers into a more long-lasting response.”

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