This is the final report in our four-part series on the cutting edge of research for treating and preventing breast cancer. Robert H. Vonderheide is a professor of medicine at the University of Pennsylvania’s Perelman School of Medicine and is the associate director of translational research at the Abramson Cancer Center there. He and Susan M. Domchek, MD, the Basser Professor in Oncology at the University of Pennsylvania, have been working together as Breast Cancer Research Foundation (BCRF) scientific investigators on developing vaccines to prevent the recurrence of breast cancer as well as novel immunotherapies for boosting the body’s ability to fight the disease.
How is immunotherapy being studied and applied as a treatment for breast cancer?
VONDERHEIDE: We believe the immune system is constantly trying to fight the development of cancer. But cancer has a way of derailing the immune system, so we need to boost the immune system with vaccines and other therapies. This approach has begun to work for patients with melanoma, lung cancer, and other cancers. We are now on the verge of making this happen for patients with breast cancer, too.
What led you to this specialty?
VONDERHEIDE: I studied immunology as a graduate student in Oxford and then decided to go to medical school so I could bring these ideas to patients. As an oncology fellow, I was fascinated by this emerging field of cancer immunotherapy, and it was during my time as a postdoc that I began to work on a preventive cancer vaccine.
DOMCHEK: My biggest goal is to prevent cancer, especially in people with BRCA1 or 2 mutations. To me, the immune system holds the power to make this a reality. We want to develop a “polio vaccine” for cancer.
Tells us about the two clinical trials you have already begun and the third that is scheduled to start
DOMCHEK: Two of these approaches are vaccines, each designed to start an immune response against the protein telomerase, which nearly every breast cancer expresses. We think telomerase is a good bull’s-eye for the immune system, and one that might work well to prevent cancer. One of these vaccines is based on a novel gene-therapy approach and in the laboratory is extremely potent.
VONDERHEIDE: The third clinical trial is another type of gene therapy in which we reengineer a patient’s own white blood cells so that they specifically target breast cancer once reinfused into the patients. At Penn, we have had success with this type of therapy in leukemia. This is the first test in patients with breast cancer.
What kinds of patients are selected to participate in your trials?
VONDERHEIDE: It varies. Two of our trials are designed for patients with metastatic disease. The other is for patients who have had their tumors surgically excised and have also completed adjuvant therapy. The vaccine is designed to prevent tumor recurrence.
What role will immunotherapy play in customizing treatment for breast-cancer patients?
DOMCHEK: There is no more personal a therapy than boosting one’s own immune system to attack cancer. One of the therapies we are testing is built by reengineering a patient’s own immune cells, so it is a separate therapy for every patient.
VONDERHEIDE: Personalized immune therapy will be different than the kind of personalized medicine in which mutations in tumors are identified and drugs are found to block those mutations. Immune therapy so far has not been restricted to a particular type of tumor mutation.
Someday in the future, can immunotherapy be utilized as a preventive tool?
DOMCHEK: A prevention vaccine is the ultimate goal of our BCRF-funded study. We hope we are just three years away from testing our new gene-therapy vaccine in healthy individuals with BRCA1 or 2 germ-line mutations who are at high risk of developing cancer. This is what I meant by a “polio vaccine for cancer.” Can you imagine the impact?
Where do you believe this path of discovery will take us as part of finding a cure for breast cancer?
VONDERHEIDE: As a colleague of mine once said, if we are going to talk about curing cancer, we will need to involve the immune system. Cancer vaccines have been difficult to use as therapy, just as a flu vaccine or pneumonia vaccine cannot treat patients who have already developed those infections. Prevention is what vaccines do best.
Are your trials open to new participants? If so, how can readers learn more about enrolling?
VONDERHEIDE: Two of the three trials are open, and the other (for patients in remission after initial surgery) will open soon. Patients or their doctors can call us for more information (800.789.7322).
