WFUBMC Mouse Study Leads to New Optimism for Advanced-Cancer Treatments

By Richard Craver, Winston-Salem Journal, N.C.

Jun. 28–By Richard Craver

JOURNAL REPORTER

Because of one hardy mouse, there’s new hope for patients with advanced forms of cancer.

Scientists at Wake Forest University Baptist Medical Center said yesterday that they will soon conduct a clinical trial that will use specific white blood cells, called granulocytes, from healthy donors to treat tumors in cancer patients.

Donors will be selected based on having an immune system that produces white blood cells which contain high cancer-fighting levels.

A similar treatment, using white blood cells from cancer-resistant mice, had a 100 percent cure rate of lab mice afflicted with advanced malignancies, the scientists said.

Zheng Cui, the lead researcher and an associate professor of pathology, yesterday revealed plans for the clinical trial at the Understanding Aging conference in Los Angeles. The study of 22 cancer patients has been approved by the U.S. Food and Drug Administration.

“Five years ago, we found this one mouse, by almost serendipity, that survived the lethal challenge of cancer cells,” Chu said in a telephone interview last week.

“By further study of the mouse, the reason it could survive, and his offspring could survive, such a lethal challenge of cancer cells is because they have very good cancer-killing activity in their white blood cells.”

Those cells had been targeted previously at fighting infection rather than cancer, Chu said.

The majority of the 500 potential donors, all needing to be healthy and under the age of 50, and the cancer patients are likely will come from the Triad and North Carolina, the scientists said.

The cost of treatment is likely to prove a barrier for some potential patients.

The scientists said that the cost for the patients to participate will be about $100,000 a patient. For patients living in many states, including North Carolina, the costs may be covered by their insurance company, according to the medical center. Donors do not receive compensation, but the scientists said it may be considered as the study progresses.

The goal of the phase II study is determining whether patients can tolerate a sufficient amount of transfused granulocytes. If the phase is successful, the scientists said they would expand the study to determine which kinds of cancers are most responsive to the treatment.

Previous laboratory tests of the cancer-fighting cells from human donors targeting cervical, prostate and breast cancer cells yielded “surprisingly good results,” the scientists said.

The study will measure the effectiveness and the level of the granulocytes in patients who have solid tumors and either didn’t respond to conventional cancer therapies or no longer respond.

“In mice, we’ve been able to eradicate even highly aggressive forms of malignancy with extremely large tumors,” Chu said. “Hopefully, we will see the same results in humans. Our laboratory studies indicate that this cancer-fighting ability is even stronger in healthy humans.”

The Baptist study holds promise for being a turning point in treating advanced cancer, said Jeff Bright, a spokesman for the North Carolina chapter of the American Cancer Society.

“There’s always hope a cancer treatment that has success in one species will work in humans,” Bright said. “Sometimes, successful therapies can come from out-of-the-box strategies. Yet there’s always a level of caution with cancer treatments because of the unknowns of the risks and potential side effects.”

Dr. Mark Willingham, a co-researcher and professor of pathology at Baptist, said that “there’s certainly the possibility that there could be something different in humans than in mice” when it comes to the effectiveness of the therapy.

“But the essay that we developed in the mice model has allowed us to do that same experiment from human white blood cells, and we’ve seen the same kind of activity,” Willingham said.

One unusual aspect of the therapy is that the scientists don’t need a perfect match for transferring the white blood cells to patients compared with typical transplant procedures.

“If we were trying to get these cells that we’re transferring in to survive for a very long time, we would have to have a perfect match so that the immune system of the patient wouldn’t reject them,” Willingham said. “We’re not trying to get (the white cells) to survive a long time.

“We rapidly begin to see, in the matter of a few hours, cancer cells dying off. That’s why we only want (the white cells) to survive very briefly.

“That has an advantage from a safety standard if that if there is some side effect that might develop from the transfer, these cells will not be there very long,” Willingham said. “Twenty years of clinical experience in doing these kinds of cell transfers has shown that it is extremely safe.”

The amount of granulocytes needed for the outpatient treatment requires a five-to-one ratio in donors to patient. The optimum time for donations is summer because most people tend to be healthier during warm weather than cold, Chu said.

Donors can give the granulocytes without losing other components of blood through a process called aphaeresis, which separates the granulocytes and returns other blood components back to donors. The process takes two to three hours.

The treatment will be given for three to four consecutive days on an outpatient basis.

The patients will be monitored closely for at least three months to measure progress on the shrinking of the tumor, and for side effects.

“Many cancer patients die in this country because they run out of conventional therapies,” Chu said. “For many of them, their only hope is new therapies. We hope this trial will add to their hope.”

—–

To see more of the Winston-Salem Journal, or to subscribe to the newspaper, go to http://www.journalnow.com/.

Copyright (c) 2008, Winston-Salem Journal, N.C.

Distributed by McClatchy-Tribune Information Services.

For reprints, email tmsreprints@permissionsgroup.com, call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.