UNC opens first clinical trial of vaccine treatment for advanced breast cancer

June 29, 2000

CHAPEL HILL -- Doctors at the University of North Carolina have opened their first clinical trial of a vaccine treatment for advanced breast cancer.

After more than four years of test tube and animal studies, researchers at UNC Lineberger Comprehensive Cancer Center will find out if intravenous infusions of their genetically engineered protein fragments will stimulate a person's immune cells to recognize and kill breast cancer cells, causing advanced breast tumors to shrink.

"This breast cancer vaccine is not a shot. It's a 'vaccine' because it should work by enhancing the patient's own immune response against their tumor," said Lineberger member Jonathan Serody, MD, associate professor of medicine and microbiology and immunology at UNC-CH School of Medicine.

"This is the first use of a vaccine directed against a modification of a specific part of the HER-2/neu protein found on breast cancer cells," he added. People have tried using engineered proteins in the treatment of melanoma but not for breast cancer." A breast cancer patient from Rochester, New York, is scheduled for her first vaccine infusion Thursday July 6, 2000.

Dr. Serody noted that current treatments, although helpful, do not cure an adequate number of women with advanced breast cancer, in which the disease has spread beyond the breast. "Often women with this disease have responses to treatment, but these are of brief duration and are not durable," he explained." he explained.

At the heart of the new treatment is the dendritic cell, a type of white blood cell that alerts the immune system to the presence of abnormal cellular proteins. The dendritic cells snatch fragments of these proteins and race to the lymph nodes to display them as targets for an immune response. Regiments of killer T-cells then proliferate, seek out and cause the destruction of cells carrying the targeted protein.

Led by Drs. Ed Collins, Jeffrey Frelinger, Roland Tisch and Jonathan Serody, the UNC research team found a way to engineer dendritic cells to target the protein HER2/Neu, which is found in tumors of about one-third of women with breast cancer. To make the vaccine, the team removes progenitor cells -- dendritic cell precursors -- from the patient's blood.

"At any one time, the percentage of dendritic cells in the bloodstream is quite small, maybe one hundredth to one thousandth of the cells in the bloodstream," Dr. Serody explained. "So we need to increase that number initially by giving the person injections of growth factor, which increases the number of immature progenitors in the blood. Then we expand those cells greatly in the lab dish by adding other proteins that allow for dendritic cell growth."

An engineered protein fragment of HER2/Neu is coupled with dendritic cells and re-infused into the patient. This molecular structure of the fragment has been changed to boost the response of T lymphocytes to kill breast cancer cells.

In the clinical trial, which is supported by the Breast Cancer Research Foundation, patients will be randomized to receive either dendritic cells coupled to the engineered HER2/Neu fragment or a fragment of the non-engineered (normal) protein.

Dosages will vary, with patients receiving escalating doses of the dendritic cells during the trial.

The treatment consists of three 30-minute infusions three weeks apart. "We anticipate two years to complete the trial, that's based on enrolling 25 individuals," Dr. Serody said. "If you respond to the treatment, you may be eligible to continue treatment for long as you want."

"We're looking for clinical regression of established tumors. By definition, this means at least a 25 percent shrinkage of established tumors," Dr. Serody said.

Serody acknowledges that the engineered protein may prove no more effective than treatment with the standard protein. This is the reason for evaluating both treatments in the trial.

Why enroll in this clinical trial? "In the setting of metastatic disease, even if the disease is stable, very few are cured," the researcher said. Less than two percent of women with advanced breast disease survive ten years after diagnosis, according to recent data.

"We believe that the vaccine can be given safely. Our hope is that by using very sophisticated techniques to monitor for an ongoing immune response against the tumor we can determine if the vaccine has a benefit in the treatment of advanced breast cancer," Dr. Serody said.

To qualify for the UNC vaccine trial requires meeting the following criteria:

Patients will not know their tissue type and this will be evaluated prior to the collection of cells for treatment. In addition, participants cannot receive chemotherapy while in the trial, although previously treatment with chemotherapy is acceptable. Participants may receive hormonal therapy during the trial.

According to Serody, this vaccine trial also marks a first for UNC Lineberger: the translation of basic research to treatment totally in-house; that is, going from test-tube to mice to humans without collaboration outside of UNC.

"Our group made the altered compound, did all the pre-clinical work in animals and are now taking this to people," the researcher said. "This is how we envision doing things in the next millennium."

As to the vaccine's future, the UNC team hopes it will see more widespread use. "We're hoping that if it shows some benefit against metastatic disease that the vaccine treatment will eventually be used earlier, for instance after chemotherapy, as an alternative treatment for women at risk for metastatic breast cancer." Serody said.
UNC-CH School of Medicine

Women interested in enrolling in the trial can contact either Dr. Serody at 919-966-6975 or call Mary Myers in the Lineberger Cancer Center protocol office, 919-966-4432.

Note: Contact Dr. Serody at 919-966-6975, email: Jonathan_Serody@med.unc.edu

University of North Carolina Health Care

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