Breast cancer vaccine clinical study complete

Ken Cowan, M.D., Ph.D.

James Talmadge, Ph.D.

Elizabeth Reed, M.D.

If it weren’t for the treatment she received for breast cancer, 78-year-old Mary Ann Tonjes of Hooper, Neb., doesn’t think she’d get to do the things she loves right now such as travel and watch her grandchildren play basketball.

Tonjes also believes that she benefited from a breast cancer vaccine study she participated in at UNMC where she received the vaccine following eight rounds of chemotherapy and 28 radiation treatments about four years ago.

“I think so far it has saved my life,” Tonjes said. “I thought it would be a good option to participate. I knew as a teaching institution, if it didn’t help me it would help someone else. Being stage III breast cancer, I would grasp at any kind of straw if that would help.”

Researchers think the vaccine may help prevent cancer recurrence. The vaccine, known as INGN 225, is a genetically engineered tumor vaccine that is made from the patient’s own cells and contains modified dendritic cells that have been artificially “infected” with a gene called p53.

P53, a tumor-suppressor gene, protects normal cells from DNA damage following exposure to sunlight and carcinogens. More than 50 percent of tumors, including breast cancer tumors, have a p53 mutation. While p53 is undetectable in normal cells, it’s over-expressed in tumors.

Following successful immunization, the vaccine theoretically “red-flags” the tumor cells as foreign and the patient’s own immune system will seek out and destroy the tumor cells that express mutant p53.

The pilot study Tonjes participated in was launched in 2005 at UNMC to determine if the vaccine is safe and effective in combination with surgery and chemotherapy in patients with early stage breast cancer that hasn’t spread. The study of 24 women also set out to find out when during treatment is the optimal time to introduce the vaccine.

UNMC was the first institution in the country to test a breast cancer vaccine made from dendritic cells, said James Talmadge, Ph.D., UNMC professor of pathology and microbiology and principal investigator of the study. The research team included UNMC physician/researchers, Elizabeth Reed, M.D., and Ken Cowan, M.D., Ph.D.

Volunteer help James Talmadge, Ph.D., who was principal investigator of the breast cancer vaccine study, said the manufacture of dendritic cells requires strict adherence to the Food and Drug Administration’s Good Manufacturing Practice (GMP) methods. The cells were sent to Moffitt Cancer Center in Florida, where the vaccine was developed based on work by Dmitry Gabrilovich, M.D., Ph.D., and is licensed to Introgen Therapeutics. Thanks to 20 healthy volunteers who donated blood for collection of white blood cells, Dr. Talmadge said UNMC is now approved to manufacture the vaccine. Vaccines must be manufactured according to FDA Good Tissue Practices (GTP) and GMP guidelines, which can be undertaken in the GMP Transplant Production Facility at UNMC. Construction on the GMP facility is estimated to be completed in May and operational in about a year. The $12.5 million facility, a joint project between UNMC and its hospital partner, The Nebraska Medical Center, will be in the Academic and Research Services building. “The Developmental Cell Processing Facility in the Lied Transplant Center has allowed us to obtain FDA approvals while we wait for the completion of GMP facility,” Dr. Talmadge said. “The ability to do these cellular protocols sets us apart from other medical centers and provides a significant resource to the state. We are able to deliver here to patients, therapeutic approaches they are unable to get anywhere else in the world.” Nancy Fulton, one of the healthy volunteers who donated cells, is personally touched by breast cancer. Her paternal grandmother died of breast cancer. One of her five sisters was diagnosed with breast cancer in August 2007 and had a double mastectomy two months later. “The quest for this research to become successful became even more personal,” she said.

The study also is unique, Dr. Talmadge said, because no other studies are looking at the timing of introducing cancer vaccines during treatment. He is hopeful future work to improve response to the vaccine will lead to an effective treatment. Two vaccines currently are effective against cancer, he said, the cervical cancer vaccine and the hepatitis B vaccine that prevents liver cancer.

Dr. Cowan, director of UNMC Eppley Cancer, said the study is important.

“It’s one of the first trials to give the vaccine to relatively early stage breast cancer patients,” Dr. Cowan said. “Overall, the vaccine was well tolerated. There were few side effects.”

Dr. Reed, associate professor of internal medicine and director of the UNMC Breast Cancer Program, said though all the data of the study isn’t yet complete, researchers have learned important information.

She said the vaccine was found safe. They also found it effective — the vaccine elicited specific T-cell responses to p53. She said the vaccine works by recognizing the mutant p53 as a marker of tumor cells, allowing a targeted immune therapy to tumor cells.

“In half of breast cancer patients, p53 doesn’t work or functions poorly,” Dr. Reed said. “The concept behind the vaccine is that it might enable the patient’s immune cells, which recognize p53, to fight off cancer cells after treatment in an attempt to prevent cancer from returning.”

The vaccine, made from a small amount of the patients’ white blood cells, was given to patients in a series of four injections. Patients were divided into two groups and given the vaccine throughout the course of their treatment with chemotherapy and radiation, or at the end of their treatment.

Dr. Reed said she and her colleagues don’t yet know if the vaccine will be a viable additional treatment for breast cancer in some women.

She said the therapy may be an important addition for treating certain high risk breast cancers.

The next step, Dr. Reed said, is to publish the results and apply for grants to continue the work.