Developing Novel Immunotherapies for Challenging Lymphomas
Todd Fehniger
MD PhDWashington University in St. Louis
Project Term: October 1, 2023 - September 30, 2028
This team science program from Washington University will develop new immunotherapy treatments for patients with hard to treat or incurable lymphomas. The team includes physicians and scientists who have developed new ideas in the laboratory for immune-based treatment, and will translate these to clinical trial testing. These include engineered natural kill cells, healthy donors T cell engineered to attack a T cell lymphoma, and lymphoma-patient specific mutations as vaccine targets.
The goal of this team science program directed by Drs. Todd Fehniger & Brad Kahl is to bring together established investigators whose research involves blood-based cancers, and to nurture collaborations among them that spark and enhance innovative translational studies with potential to improve patient care. This will be accomplished through three distinct projects as well as research core infrastructure.
The first project is led by Todd Fehniger and Brad Kahl, MD, and involves engineering the immune system’s natural killer (NK) cells to target specific lymphoma cells. The researchers will expose the natural killer cells to a chemical cocktail that activates the cells inducing changes that allow the NK cells to respond more effectively. They also will genetically engineer the cells to add a receptor that specifically targets B cell lymphoma. The engineered cells are called chimeric antigen receptor NK cells (CAR-NK cells), and they use a similar strategy as CAR-T cells to target specific tumor cells. However, these CAR NK cells are not expected to result in the serious side effects that can occur with CAR T cells.
A second project is led by DiPersio and Michael Rettig, PhD, and involves gene editing of therapeutic T cells to kill cancer while preventing the T cells from targeting the patients’ own healthy cells. In this study, these “universal” CAR-T cells will be used to treat T cell cancers — including T cell non-Hodgkin’s lymphoma and T cell acute myeloid leukemia — while also preventing graft-versus-host disease. The researchers will investigate how to help the therapeutic T cells persist longer in the body and enhance their cancer-killing capacity.
The third project is led by Robert Schreiber, PhD; Obi Griffith, PhD; Nancy Bartlett, MD; and William Gillanders, MD, will target B cell non-Hodgkin lymphoma. The researchers will develop individualized vaccines that stimulate and direct the immune system to kill a patient’s cancer cells. Cancer cells often produce unusual proteins on their surfaces. Vaccines that train the immune system to recognize these abnormal proteins — proteins that are always unique to a patient’s specific cancer — help the immune system identify and target the cancer cells for elimination.