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Elizabeth M. Jaffee, MD, FAACR, FACP
Dana and Albert “Cubby” Broccoli Professor of Oncology
Deputy Director, The Sidney Kimmel Comprehensive Cancer Center
Co-Director of the Gastrointestinal Cancers Program
Johns Hopkins University
Goal: To advance the use of immunotherapy in breast cancer with combination approaches for patients with recurrent HER2-positive breast cancer.
Impact: Drs. Jaffee and Emens are pursuing ways to enhance the response of immunotherapy so that more patients can benefit from it.
What’s next: The team will test whether a combination immunotherapy approach will improve response to immunotherapy in HER2-positive breast cancer.
Immunotherapy is a promising treatment for breast cancer, but as with other anti-cancer therapies, tumors are able to evade these drugs and block their effects. Drs. Jaffee and Emens are focused on developing immunotherapy combinations that convert non-responding tumors to responders, enhance responses that do occur, and overcome acquired resistance to immunotherapy.
Full Research Summary
Research area: Developing potent immunotherapy combinations for patients with recurrent HER2-positive breast cancer.
Impact: While some breast cancer patients respond to a type of immunotherapy called checkpoint inhibitors, these drugs have not been very effective in treating patients with HER2-positive breast cancer. Drs. Jaffee and Emens have identified additional checkpoint targets and are investigating combination immunotherapy treatments that induce T cells and counter the tumor’s immunosuppressive properties so that more patients will be able to benefit from immunotherapy.
Current research: The team has been conducting laboratory studies of the combination of anti-PD-L1 immunotherapy agent atezolizumab with the chemotherapy drug nab-paclitaxel in laboratory models of advanced HER2-positive breast cancer. The same treatment combination was recently FDA-approved for the treatment of advanced triple negative breast cancer. This year they are also studying another immune target called TIM-3, which they believe is blocking the effect of anti-PD-L1 treatment. They will measure protein levels of TIM-3 in human tumors as well as laboratory models and begin testing combination approaches to target TIM-3 and PD-L1.
What they’ve learned so far: Drs. Emens and Jaffee found that when the checkpoint protein, PD-L1 was blocked in their laboratory models of HER2-positive breast cancer, a counter effect occurred to decrease the anti-PD-L1 treatment. They found that another checkpoint protein, called TIM-3 may be blocking the cancer killing ability of T-cells activated by the PD-L1 therapy.
What’s next: The team will continue studying the presence of TIM-3 in tumors and test whether targeting TIM-3 in addition to PD-L1 results in more effective response.
Dr. Jaffee is an internationally recognized expert in cancer immunology and pancreatic cancer. She is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-Director of the Skip Viragh Pancreatic Cancer Center and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focus is on developing novel immunotherapies for the treatment and prevention of pancreatic cancer. Dr. Jaffee is a Past President of AACR. She has served on a number of committees at the National Cancer Institute including co-chair of the Blue Ribbon Panel that provided scientific advice to Vice President Biden’s Moonshot Initiative. She currently serves as chair of the National Cancer Advisory Board and Chief Medical Advisor to the Lustgarten Foundation for Pancreatic Cancer Research. She is the inaugural Director of the new Convergence Institute at Johns Hopkins. She was recently elected to the National Academy of Medicine and is a Fellow of the American College of Physicians.