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Robert H. Vonderheide, MD, D.Phil
Director, Abramson Cancer Center
John H. Glick, MD Abramson Cancer Center Director’s Professor
Vice Dean, Cancer Programs, Perelman School of Medicine
Vice President, Cancer Programs, University of Pennsylvania Health System
University of Pennsylvania
Goal: To develop new immune therapies for breast cancer patients.
Impact: Dr. Vonderheide is conducting trials of several immune-based approaches for prevention and treatment of breast cancer, with a particular focus on a vaccine that may protect those with inherited mutations in the BRCA1 and BRCA2 genes from developing the disease. His work may reveal new opportunities for immunotherapy for patients with breast cancer and those with a high breast cancer risk.
What’s next: Having recently achieved positive results in three trials (including one of the vaccines), he and his team will now test their effectiveness in larger studies.
Immunotherapy is a type of treatment that stimulates the immune system to fight cancer. While it has been effective in improving long-term outcomes in those with certain types of cancer such as melanoma and lung cancer, relatively few breast cancer patients benefit from immunotherapy. Dr. Vonderheide is exploring and testing new ways to make breast tumors more responsive to immunotherapy, and he is also working on a vaccine that would protect those at high risk of breast cancer from developing the disease.
Full Research Summary
Research area: Developing immune therapies for patients with breast cancer.
Impact: Immunotherapy has been effective in some types of cancers including some triple-negative breast cancers, but most breast cancer patients have not benefited from current immunotherapies. Dr. Vonderheide’s research is focused on developing immunotherapies that stimulate a patient's own immune system to recognize and destroy cancer cells effectively. He and his team are conducting studies that will reveal opportunities for new immunotherapies and prevention strategies for patients and high-risk individuals.
Current investigation: Dr.Vonderheide’s team is investigating the immune response in human breast cancer patients, with the goal of developing and testing a novel vaccine that may prevent breast cancer in healthy but high-risk individuals.
What he’s learned so far: He and his colleagues have conducted a series “proof-of-concept” clinical trials designed to reveal new opportunities for immunotherapy for patients with metastatic breast cancer or breast cancers that could benefit from radiation therapy in combination with immunotherapy. In the last year, three clinical trials were completed or nearly completed – these include:
- Testing genetically engineered immune cells -T cells which were designed to destroy breast cancer cells .
- Testing a DNA vaccine which was designed by Dr. Vonderheide’s group for high-risk patients in remission after adjuvant therapy and healthy carriers of mutations in BRCA.
- Testing specialized radiation therapy in combination with dual checkpoint blockade therapy (PD-L1 and CTLA4)
Dr. Vonderheide and his colleagues obtained promising results from these clinical trials and these approaches will be moved to larger clinical trials. In fact, the larger DNA vaccine trial has been approved by the FDA to study healthy individuals carrying mutations in BRCA1 or BRCA2 – the first ever prevention vaccine in this high-risk population.
What’s next: Dr. Vonderheide and his team will continue to expand on research from their immunotherapy-focused clinical trials. The next exciting step toward cancer prevention will be testing their DNA vaccine in a larger population of high-risk healthy individuals carrying mutations in BRCA1 or BRCA2 genes.
Robert H. Vonderheide, MD, DPhil, is the Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center’s Director Professor in the Perelman School of Medicine. He is Vice Dean for Cancer Programs at PSOM and Vice President of Cancer Programs for the University of Pennsylvania Health System. He serves as Lead Physician for the Cancer Service Line of the Health System.
Dr. Vonderheide graduated from the University of Notre Dame (Chemical Engineering) and obtained his DPhil in immunology from Oxford University as a Rhodes Scholar. He graduated from Harvard Medical School and completed a residency in Internal Medicine at the Massachusetts General and a fellowship in medical oncology at the Dana Farber. As an NIH-funded investigator at Penn Medicine, Dr. Vonderheide directs a research team focused on cancer immunology and immunotherapy. He has published more than 160 peer-reviewed manuscripts with senior-author papers in high-impact journals such as Science, Nature, Cancer Cell, and the New England Journal of Medicine. He is well-known for deciphering the immune mechanisms of CD40 activation in cancer and directing clinical trials of novel immunotherapy.
Nationally, Dr. Vonderheide is a member of the National Cancer Institute Board of Scientific Advisers, the National Comprehensive Cancer Network Board of Directors, and serves as Deputy Editor of Cancer Immunology Research. He is an elected member of the American Society of Clinical Investigation (serving on the ASCI council from 2014-2017) and American Association of Physicians.
BCRF Investigator Since
The Leonard and Judy Lauder Fund Award