One of the key objectives of the Foundation is to provide funding for research to prevent, treat and cure Graft vs. Host Disease.
In 2019, the Foundation provided a designated Grant through the Leukemia Lymphoma Society (LLS) to Dr. Ivan Maillard, MD, PHD. We are very pleased that our grant is being put to very good use by Dr. Maillard. Below is an update from the LLS describing the progress that is being made with his research.
A sincere thank you to the LLS and Dr. Maillard for helping the Meredith A. Cowden Foundation work to fulfill a key part of its Mission.
Medical progress and philanthropy are inextricably linked: Visionary scientists can only realize their breakthrough ideas with the partnership of visionary donors. The critical role of philanthropy took on an even greater importance in the past year as the financial impact of the COVID-19 pandemic reverberated through our nation. Thanks to your generous support, The Leukemia & Lymphoma Society (LLS) maintained its commitment to moving science forward, despite this financial downturn and the upheavals and uncertainty of the pandemic. Although LLS was in the difficult position of having to make strategic cuts to our research investments, your contribution to our program enabled us to sustain promising science through this crisis.
We are pleased to provide you with the following Impact Report on the research of Dr. Robert Ivan Maillard which continues to advance thanks to your support. Thank you for being such a valued partner in our mission to improve care for patients and deliver new hope to them and their families.
Progress in the Research of Ivan Maillard, MD, PhD
University of Pennsylvania Medical Center
Preclinical Notch inhibition to prevent graft-versus-host disease in mice and nonhuman primates
Patients battling blood cancers are often treated with bone marrow transplantation. In some cases, however, the donor immune cells attack the recipient’s cells, causing graft-versus-host disease (GVHD), one of the most dangerous complications of bone marrow transplantation. Despite preventive treatments, many patients experience acute GVHD, which can be life-threatening, or chronic GVHD, which can trigger long-term complications and decrease a patient’s quality of life.
To address the need for better therapies for prevention and treatment of GVHD, Dr. Ivan Maillard is developing a new strategy that works by blocking signals delivered to immune cells soon after transplantation. Specifically, Dr. Maillard is conducting animal studies and examining different approaches to inhibit signaling in the Notch pathway, which has been shown to play a role in GVHD. His approach involves an antibody called anti-DLL4, which targets the Notch pathway in a way that is different from other treatments tested. In animal studies, anti-DLL4 antibodies preserved beneficial aspects of bone marrow transplantation, including anti-tumor effects. A single dose of the agent when given immediately prior to transplantation provided long-term protection from GVHD in mouse models.
In the past year, Dr. Maillard and his team continued their preclinical experiments in mice and non-human primates, which are providing critical information to guide the deployment of new treatments based on inhibition of the Notch signaling pathway that prevent graft-versus-host disease. They have gathered new information to understand the mechanisms by which Notch inhibition provides high protection from intestinal graft-versus-host disease, the most dangerous aspect of this complication. Using this new understanding, they also tested two possible treatment combinations that did not have the ideal profile of activity in non-human primates. With this information, they are now developing and testing other treatment combinations to identify the optimal path towards the development of a human clinical trial.
Taken together, these advanced preclinical experiments will lead to the to identification of the most promising strategies to develop new treatments that selectively prevent graft-versus-host disease in patients.