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Elizabeth M. Jaffee, MD
Professor of Oncology
Johns Hopkins University
- Seeking to advance the use of immunotherapy in breast cancer with combination approaches for patients with recurrent HER2-positive breast cancer.
- Laboratory studies are ongoing to test a combination treatment to improve response to immunotherapy.
- These studies may lead to clinical trials of potent immunotherapy combinations for patients with recurrent HER2-positive breast cancer.
Advancements in immunotherapy have made it a promising treatment approach for some cancers, but as with most other cancer therapies, tumors can outsmart immune-based drug and block their effects. Drs. Jaffee and Emens are testing combination approaches that prevent the tumor from hiding from immune surveillance and make immunotherapy more effective.
Full Research Summary
Cancer immunotherapy is a new treatment approach that enlists the patient's own immune system to fight cancer. Monoclonal antibodies that block the PD-1 immune checkpoint (called checkpoint inhibitors) unleash a robust anti-tumor immunity response in a broad range of tumors.
Although some breast cancer patients respond to PD-1 blockade, the majority do not respond. Moreover, most of the trials testing PD-1/PD-L1 modulators in breast cancer have been in the triple negative breast cancer subtype.
As yet, there has been little efficacy reported of checkpoint inhibitors for HER2-positive breast cancer. This may be due to a lack of specialized immune cells (called T cells) at the tumor sites. Strategies that induce T cells and counter the tumors’ immunosuppressive properties will be required for immunotherapy to work in most breast cancer patients.
In previous work, Drs. Jaffee and Emens showed that adding PD-1 pathway blockade plus an additional immune-based treatment can increase T cell production and increases tumor-free survival in laboratory models of HER2-positive breast cancer. However, this therapy also activates pathways that shut down the anti-tumor response. They have identified two potential targets to counter this effect. Over the next year, they will focus on targeting the immunosuppressive molecules to increase the efficacy of combination immunotherapy.
They hope to develop a highly active immunotherapy regimen that will translate into a clinical trial, testing the most potent combination immunotherapy regimen in patients with recurrent HER2+ breast cancer.
Dr. Jaffee is an internationally recognized expert in cancer immunology with specific expertise in the pre-clinical and early clinical development of immunotherapies for breast and pancreatic cancers. She has developed novel vaccine approaches for the treatment of pancreatic and breast cancers and new methodologies for identifying vaccine induced T cell and antibody targets. Dr. Jaffee serves Co-Director of the GI Cancers Program at Johns Hopkins School of Medicine and Associate Director for Translational Science in the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She directs the Cell Processing and Gene Therapy cGMP Facility and is Deputy Director for the Institute for Translational and Clinical Research. Recent appointments include: National Cancer Advisory Board, 2015 AACR Annual Meeting Program Planning Committee, Scientific Advisory Council for the Cancer Research Institute and Team Leader for Stand Up To Cancer Pancreatic Dream Team.