Leveraging T-Cell Metabolism to Improve Anticancer Immunotherapies
Abstract
Leukemia is one of the most common blood cancers in both children and adults, and despite advances in cancer treatments, difficult-to-treat leukemia remains fatal for many people. Multiple myeloma is another prominent blood cancer in adults, whose treatment has remained very challenging. Over the last decade, researchers have begun to use the immune system to fight cancer, taking advantage of the fact that immune cells can be taught to see cancer cells as "foreign" and then attack and destroy them. This breakthrough has revolutionized cancer care for many individuals and given hope where none existed before. However, this treatment is not perfect. In up to 30% of cases, immune cells that are given to the patient do not stick around. And when these cells disappear, it is very likely that the cancer will return. We would like to change this situation by getting immune cells to stay around longer. By doing this, the immune cells can do a better job of keeping the cancer cells in check. Our plan is to give the immune cells metabolic proteins that will help them survive longer when they get transferred to the patient. Based on this plan, our research falls under the FY18 PRCRP Topic Area of Immunotherapy, but also impacts the treatment of Blood Cancers and Myeloma. Ultimately, our research will help patients suffering from multiple myeloma and difficult-to-treat leukemia. It will do this by providing a therapy that is more effective than current therapies for treating their disease. The potential clinical application of this research would be for a patient with high-risk leukemia, perhaps someone who has failed other treatment options, to come into the clinic and receive engineered immune cells. However, in addition to the standard engineering, these immune cells would also be super-charged with a metabolic protein to help them survive longer after they are given back to the patient, effectively providing better leukemia control. A potential risk would be to make the immune cells "too active," but we can also engineer shutoff switches to remove the engineered cells if they become too energetic. These studies are in the late, preclinical stages of development. This means that once the proposed studies are accomplished, we will be ready to move this technology into clinical trials. Because it will take 2 years to complete the current research, and another 1 to 2 years to design the clinical trial, we expect that our research will achieve a clinically relevant outcome in the next 3 to 5 years. In the end, this study will contribute to cancer research by demonstrating a new way to optimize immune cell responses against cancer, a finding that could apply to many different treatment options for many different cancers. From a patient-care standpoint, these innovations have the potential to better control leukemia and multiple myeloma in patients who are failing our current, cutting-edge therapies. Development of both leukemia and multiple myeloma are known side effects of exposure to ionizing radiation, a FY18 PRCRP Military Relevance Focus Area. These studies are thus, extremely relevant to active duty Service members who are exposed to the hazards of ionizing radiation while serving our country. In addition, as they age, Veterans become less tolerant of harsh cancer treatments. Having the immune system fight cancer is often better tolerated than traditional chemotherapy, so optimizing immunotherapies will make a safer alternative even more attractive for our older Veterans. Finally, immunotherapy has worked phenomenally well in children with high-risk leukemia. Improvements in this technology will further allow active duty Service members whose children suffer from blood cancers, to more readily focus on their military duties, knowing that their loved ones are receiving the most optimized care possible.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910291
Entities
People
- Craig Byersdorfer
Organizations
- United States Army
- University of Pittsburgh