Newswise — A one-of-a-kind breast cancer vaccine trial—this one focusing on patients with non-metastatic disease—is under way at the University of Nebraska Medical Center. Most cancer vaccine trials have focused on patients with late-stage cancer that has spread from the initial tumor site. But UNMC researchers believe giving a vaccine earlier may produce a more powerful response from the patient's immune system against the cancer.

The goal of this breast cancer vaccine is to cause regression of remaining disease following standard therapy, and ultimately to prevent a recurrence.

What's different about this vaccine

The breast cancer vaccine being studied at UNMC differs from other breast cancer vaccines in several important ways: 1) it's being given to cancer patients earlier in their disease, 2) the vaccine contains modified dendritic cells believed to be more effective in attacking the cancer, 3) these dendritic cells have been artificially infected with a gene called P53 found in everyone's body, and 4) because the vaccine contains a common protein, it would be more economical to produce. Most other breast cancer vaccines are created only after researchers identify a mutant peptide specific to an individual's cancer.

Why dendritic cells are important

Dendritic cells are found in all organs of the body. They grab antigens, or identif proteins found on the surface of cells, and wave the antigens like red flags, as a signal to the immune system. The immune system's T-cells recognize the antigens from viruses, bacteria and other organisms as foreign and dangerous and mount an attack against them. But since the immune system doesn't perceive cancer cells as foreign or "non-self," this built-in detection system doesn't work against cancer.

The vaccine being used in the UNMC pilot study contains modified dendritic cells that will theoretically red-flag the tumor cells as foreign and destroy them.

"We believe a cancer vaccine created from dendritic cells in the blood may be the most effective way to induce an immune response to fight breast cancer," said Ken Cowan, M.D., Ph.D., Director of the UNMC Eppley Cancer Center.

The importance of P53 in producing a robust immune response

The modified dendritic cells have been infected with the P53 protein, a well studied tumor-suppressor gene commonly referred to as the "guardian of the genome." P53 protects normal cells from DNA damage following exposure to sunlight and carcinogens.

"But P53 is also the most commonly mutated gene in cancers," Dr. Cowan said. "More than 50 per cent of all cancer patients, including those with breast cancer, have a P53 mutation. While P53 is undetectable in normal cells, it's over-expressed in tumors. And patients whose tumors show a mutation of the P53 gene have a greater risk of cancer recurrence.

"Because our vaccine contains the entire P53 protein, we believe it may stimulate a more robust immune response to fight the cancer than we've seen with previous vaccines," Dr. Cowan said.

The UNMC breast cancer vaccine protocol was developed by Dr. Cowan, James Talmadge, Ph.D., professor of pathology and microbiology at UNMC, and Elizabeth Reed, M.D., associate professor of internal medicine and director of the UNMC Breast Cancer Program.

The goal

Dr. Reed said the goal of the vaccine is to interrupt the cancer cycle sooner and create a better chance for a cure. "Most vaccines are given to patients with metastatic illness, but that may not be the 'best' time," said Dr. Reed. "A patient's immune system is often overtaxed during metastatic cancer by extensive tumor burden and treatments like chemotherapy. So we're aiming our breast cancer vaccine trial at newly diagnosed patients who have earlier disease and limited tumor burden. These patients are typically healthier than those who have metastatic disease, but they are still at increased risk of cancer recurrence."

To make the vaccine, patients in the study will have a small amount of their white blood cells, or lymphocytes, removed through a process similar to blood donation called leukopheresis. The lymphocytes are turned into dendritic cells in the laboratory, and infected with the P53 protein through a viral vector.

Study patients will get the vaccine in a series of four injections. The patients will be randomized to receive the vaccine throughout the course of chemotherapy and radiation, or they will get all doses of the vaccine at the end of their treatment. The goal is to find out when during the course of treatment the vaccine produces the best response from the patient's immune system.

UNMC seeks to enroll up to 50 breast cancer patients for this pilot study. Dr. Reed emphasized this is the only site in the country using a breast cancer vaccine made from dendritic cells. Moffitt Cancer Center in Florida is also conducting a vaccine trial using dendritic cells, but that trial is focusing on patients with lung cancer. Appropriate candidates for this breast cancer vaccine trial include:--Only newly diagnosed patients. The study will accept patients who've had surgery to remove the cancer, but if a patient has had any prior chemotherapy or radiation, she is not a candidate.--Patients must have tumor expression for the P53 gene mutation --Patients cannot have metastatic illness.--Patients must have four positive lymph nodes or tumors larger than 3 centimeters.

If you're interested in learning more about qualifying for this study, please call 402-559-5582.

The UNMC Eppley Cancer Center is a National Cancer Institute designated cancer center -- a distinction held by only 61 centers in the country. The UNMC Eppley Cancer Center is one of the 17 founding members of the National Comprehensive Cancer Network, an alliance of the world's leading cancer centers.