Preclinical Efficacy of Daratumumab in T Cell Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a form of cancer of the white blood cells, caused by the overproduction and accumulation of cancerous cells known as lymphoblasts. These lymphoblasts can arise from two different cell types known as T or B cells (designated as T-ALL or B-ALL). Both comprise the most common cancer among children and is the most frequent cause of death from cancer before 20 years of age. T-ALL is a particularly aggressive cancer, with fewer options for novel treatment strategies.
The use of immunotherapy is an effective approach to fight cancer cells, which involves empowering the immune system to kill cancer cells. One approach includes the use of proteins called monoclonal antibodies that specifically bind to cancer-specific targets expressed on the cell surface that induces an immune response against the cancer cell. Daratumumab is a monoclonal antibody that recognizes a target known as CD38, and has been effective for patients with another cancer, multiple myeloma. We have evidence of CD38 expressed at high levels on a broad panel of both B- and T-ALL, while normal cells express low levels of CD38. Therefore, CD38 is a potentially valuable target in the development of immunotherapy for T-ALL
We have preliminary evidence demonstrating that daratumumab dramatically decreases T-ALL cancer cells in human-derived animal models. We propose to further test daratumumab for T-ALL. We believe this project has great likelihood of directly translating into therapy for children with T-ALL in the very near future.