Todd Bradley, PhD
Director, Immunogenomics, Genomic Medicine Center; Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full BiographyTodd Bradley, PhD, Genomic Medicine Center, received a one-year, $50,000 2023 Pilot Award from The University of Kansas Cancer Center.
Dr. Bradley’s study, “Dual-targeting Immunotherapy to Target B-cell Lymphoma,” will build on current therapies that use the patient’s own immune cells to engineer chimeric antigen receptor T (CAR-T) cells that are supercharged to kill cancer. Typically, these therapies recognize one target on the cancer cell, but Dr. Bradley is developing CAR-T cells to recognize two targets on lymphoma cells, in an effort to provide more effective targeting and killing of B-cell mediated cancers.
As Dr. Bradley explains, combination chemotherapy and immunotherapy that targets the CD19 or CD20 receptors has significantly improved overall survival rates of lymphoma. Despite this success, though, there are a percentage of patients that do not respond to therapy, or who relapse after treatment with this chemo-immunotherapy. This is usually because the lymphoma cells do not express the CD19 or CD20 on the cell surface, or lose expression over time, making the immunotherapeutics not effective. When this happens, there is a lack of targeted therapeutic options available, and survival outlooks are poor.
To solve this problem, Dr. Bradley and his team seek to engineer immunotherapies against lymphoma that target two receptors on the cancer instead of one, making it harder for the cancer to escape from the immunotherapy. Using genomics tools studying B cells, Dr. Bradley identified two additional receptors that frequently are expressed in lymphoma. The team engineered monoclonal antibodies that target these new receptors along with the CD20 receptor and showed that they could recognize and kill lymphoma cells. Importantly, they showed these dual-targeting antibodies could kill lymphoma cells that are resistant to one immunotherapy alone.
The team will build upon the results of these previous studies to create two new dual-targeting CAR-T cell immunotherapies with the intent of demonstrating the effectiveness of these modalities in recognizing and killing lymphoma cells.
Their hope is that, by targeting two surface receptors on lymphoma cells, it will result in superior recognition and toxicity to cells of lymphoma that have escaped conventional therapies.
“The impact of this work should be the identification of new immunotherapy tools that can be directly translated into the clinic to combat treatment resistance in lymphoma and other B-cell mediated diseases, thus creating a new hope for alternative targeted immunotherapy in these patients.” said Dr. Bradley.
Doug Myers, MD, and John Perry, PhD, Hematology/Oncology/BMT, are co-investigators on the study.
The University of Kansas Cancer Center’s Pilot Awards fund promising novel research being conducted by cancer center members.