University of Nebraska Medical Center researchers are conducting a unique vaccine trial for breast cancer patients with non-metastatic disease. Researchers believe giving the vaccine to patients at an earlier stage of cancer may produce a better chance of preventing a recurrence and cause regression of any remaining disease.
The vaccine is also unique in that it’s made from the patient’s own dendritic cells. “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.
Dendritic cells are found in all organs of the body. Their purpose is to grab antigens, or identifying proteins found on the surface of cells, and to 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 new breast cancer vaccine, developed by Dr. Cowan, and James Talmadge, Ph.D., professor of pathology and microbiology at UNMC, along with Dmitry Grabilovich, M.D., Ph.D., from the Moffitt Cancer Center in Florida, contains “modified” dendritic cells. The cells have been artificially “infected” with a gene called P53.
P53 is a well studied tumor-suppressor gene and is commonly referred to as the “guardian of the genome.” It 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. Patients whose tumors show a mutation of the P53 gene have a greater risk of cancer recurrence. This vaccine trial is only open to breast cancer patients who show a P53 mutation.
“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.
While P53 is undetectable in normal cells, it’s overexpressed in tumors. The vaccine will theoretically “red-flag” the tumor cells as “foreign” and destroy them.
In the past, Dr. Cowan said most breast cancer vaccines were created after researchers identified a mutant peptide specific to an individual’s cancer. While developing a vaccine specific to each patient isn’t economically feasible, the vaccine under study at UNMC contains a protein, P53, found in everyone’s body.
Elizabeth Reed, M.D., associate professor of internal medicine and director of the UNMC Breast Cancer Program, 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.”
UNMC is seeking 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.
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. The vaccine is then given to patients in the study in a series of four injections. The patients will be randomized to receive the vaccine through-out the course of their treatment with chemo-therapy 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.
Appropriate candidates for this breast cancer vaccine trial include:
–Only newly diagnosed patients. If a patient has had any prior treatment, she is not a candidate.
–Patients must have tumor expression for the P53 gene mutation or accumulation.
–Patients cannot have metastatic illness.
–Patients must have four positive lymph nodes or tumors larger than 3 centimeters.
For more information, call 559-5582.
UNMC is the only public health science center in the state. Its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through its commitment to education, research, patient care and outreach, UNMC has established itself as one of the country’s leading centers in cancer, transplantation biology, bioterrorism preparedness, neurodegenerative diseases, cardiovascular diseases, genetics, biomedical technology, ophthalmology and arthritis. UNMC’s research funding from external sources is now more than $76 million annually and has resulted in the creation of more than 2,400 highly skilled jobs in the state.
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