2021 A Breath of Hope Research Award Recipient
Kipp Weiskopf, MD, PhD from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts
A Breath of Hope is honored to announce our 2021 Peg Fisher-Jullie Fight For Life Award winner — Dr. Kipp Weiskopf from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. Dr. Weiskopf’s winning proposal focuses on the interaction between EGFR mutant lung cancer cells and the immune system.
Kipp Weiskopf, MD, PhD:
Dr. Weiskopf began his scientific career as an undergraduate student at Amherst College in Amherst, MA. After graduating, he was awarded a Churchill Scholarship and earned an M.Phil. degree from the University of Cambridge. In the laboratory of Dr. David Glover, he studied the fundamental process of cell division.
Dr. Weiskopf subsequently attended Stanford University and earned an M.D. and a Ph.D. in Cancer Biology as a member of the Medical Scientist Training Program. For his graduate studies, he conducted research in the laboratory of Dr. Irving Weissman, a pioneer of immunology, stem cell biology, and cancer immunotherapy. Dr. Weiskopf studied the role of the CD47/SIRPa axis in regulating macrophage responses to cancer, and he helped define this interaction as a macrophage immune checkpoint.
After completing his studies at Stanford University, Dr. Weiskopf trained as a resident in Internal Medicine at Brigham and Women’s Hospital in Boston, MA. He is now a member of the Hematology and Oncology Fellowship program at Dana-Farber Cancer Institute in Boston, MA.
In 2019, Dr. Weiskopf was appointed as a Whitehead Fellow at Whitehead Institute for Biomedical Research in Cambridge, MA. He currently leads a laboratory that studies how macrophages interact with cancer cells with an emphasis on the development of novel immune-based therapies for cancer.
Dr. Weiskopf is an inventor on more than a dozen U.S. patents related to macrophage-directed therapies. He co-founded a biotechnology company, ALX Oncology, to help advance CD47-blocking therapies for the benefit of patients with cancer. He currently serves on the company’s scientific advisory board.
About the Project:
Dr. Weiskopf’s research project funded by A Breath of Hope Lung Foundation focuses on the interaction between EGFR mutant lung cancer cells and the immune system.
Although therapies that activate the immune system have been effective for some types of cancer, their use remains limited for EGFR mutant lung cancer. Prior studies have mainly focused on immunotherapies that target T cells and the PD-1/PD-L1 axis.
In contrast, this project will investigate how immune cells called macrophages can be used to attack and eliminate EGFR mutant lung cancer cells. Macrophages are often the most common immune cells in tumors, and they can be provoked to attack cancer cells when provided with an appropriate stimulus.
This study will investigate how macrophages can be activated to enhance conventional therapies for EGFR mutant lung cancer. The goal of this research is to provide the scientific rationale for testing these therapeutic strategies in patients with EGFR mutant lung cancer.
Targeting Macrophages to Eliminate EGFR Mutant Lung Cancer, Principal Investigator: Kipp Weiskopf, M.D., Ph.D.
August 2022 Progress Report:
We continue to make progress towards our overall scientific goals. In the reporting period, we have performed experiments to understand how EGFR mutant lung cancer cells evade detection by the immune system. We have identified new signals that are present on some EGFR lung cancer cells that help the cells avoid being “eaten” by macrophages in a process known as phagocytosis. We are performing ongoing experiments to block the function of these signals to determine whether they could be novel drug targets for EGFR mutant lung cancer.
We have also continued to advance our studies using mouse models of EGFR mutant lung cancer. We found that EGFR inhibitors can be enhanced by certain therapies targeting macrophages. These findings may translate to other types of driver mutations in lung cancer, such as ALK fusions or KRAS mutations. Overall, we believe our findings provide the scientific rationale for new clinical trials testing combination therapies for patients with EGFR mutant lung cancer.
February 2022 Progress Report:
During the reporting period, we have continued our studies to examine ways to stimulate immune cells called macrophages to attack and eliminate EGFR mutant lung cancer cells. We have focused the majority of effort on evaluating the combination of lung cancer cells and macrophages in petri dishes. We have combined EGFR mutant cancer cells and macrophages together with different drug therapies and then measured the growth of the cancer cells over time. We have found that certain combinations of drugs can make the cancer cells more vulnerable to being engulfed and destroyed by macrophages. This combination strategy seems to be effective when we test multiple different specimens, including established EGFR mutant lung cancer cell lines or patient-derived specimens. We have also begun to investigate whether the combination strategy can be effective when administered in mouse models of cancer. In collaboration with the laboratory of Dr. Aaron Hata at Massachusetts General Hospital, we have found that our combination strategy may enhance the ability of the immune system to recognize EGFR mutant lung cancer cells as foreign and fight them off. We will continue to study this combination strategy in the upcoming award period in additional cell culture models and mouse tumor models.
August 2021 Progress Report:
The goal of cancer immunotherapy is to stimulate a patient’s own immune system to recognize tumors as foreign and eliminate them from the body. Tremendous success has been achieved using drugs that activate immune cells called T cells to attack cancer. However, the majority of patients do not benefit from these therapies, and there is a critical need to discover safer and more effective ways to use the immune system to fight cancer. This seems to be particularly true for patients with EGFR mutant lung cancer, where immunotherapy has not yet been successful.
Immune cells called macrophages are often the most common immune cell found in tumors, and they can be prompted to attack cancer cells when provided with an appropriate stimulus. Macrophages can attack cancer cells by engulfing and destroying them—a process known as phagocytosis. The main goal of our study is to identify ways to use macrophages to attack and eliminate EGFR mutant lung cancer. As a first step to achieve this goal, we have developed a culture system in which EGFR mutant lung cancer cells are combined with human macrophages in petri dishes. Using this system, we can add different drug treatments and measure which therapies and combinations are most effective at coaxing the macrophages to attack the cancer cells. We have determined that targeted therapies may make EGFR mutant lung cancer cells particularly vulnerable to macrophage attack. This is especially true for cells that become resistant to targeted therapies. In the upcoming award period, we will test whether these concepts hold true in mouse models of EGFR mutant lung cancer. We hope that these studies will serve as a stepping stone to investigate new drug combinations in patients with EGFR mutant lung cancer.