
Researcher Profiles

Craig T. Jordan, Ph.D.
2018 Grant Recipient
CD123 CAR T cell therapy for the treatment of patients with Myelodysplastic Syndrome
Discovery Research Grant 2018
PROJECT SUMMARY
Myelodysplastic Syndromes (MDS) are a group of bone marrow disorders where abnormal cells replace the bone marrow, causing insufficient production of healthy blood cells. In most cases, MDS eventually results in death and/or evolves to more acute forms of blood cancer such as leukemia, which are also frequently lethal. Current treatment options for MDS patients are very limited and improved therapies are urgently needed.
To date, one of the more effective ways to treat MDS is via an allogeneic bone marrow transplantation (BMT) procedure, which represents a form of so-called “cellular therapy”. This type of therapy works when healthy stem and immune system cells from a BMT donor are administered to an MDS patient where they destroy diseased cells and replace the marrow. Unfortunately, BMT has serious side effects, and can only be used in relatively young and healthy patients. The majority of MDS patients are not suitable candidates for BMT.
Recently, a much more sophisticated form of cellular therapy has been developed. In this approach, immune cells from cancer patients or healthy donor can be engineered in the laboratory to be much more effective in recognizing and killing malignant cells. The approach is termed CAR (chimeric antigen receptor) T-cell therapy. For the treatment of acute leukemia, several recent studies have shown that appropriately engineered CAR T-cells can provide remarkable results, in some cases leading to full clinical remissions. Thus, as a form of immunotherapy, CAR T-cells represent a major medical advance. Using funding from a previous Evans Foundation grant we performed laboratory studies to investigate the possibility of using CAR T-cell therapy for MDS patients. We were able to successfully create CAR T-cells that can eradicate MDS cells in several laboratory models. Based on those findings, we now propose to conduct a clinical trial in which high risk MDS patients will be treated with CAR T-therapy. The approach involves isolating normal T-cells from the blood of patient. Engineering those cells in the laboratory to possess the chimeric antigen receptor (CAR), and then returning those cells to the bloodstream of the patient. If successful, the CAR T-cells will home to and destroy MDS cells. Based on findings to date with other forms of blood cancer, we believe that CAR T-cell therapy is a very exciting new option for MDS patients.
PUBLICATIONS
Brett M. Stevens, Wei Zhang, Daniel A. Pollyea, Amanda Winters, Jonathan Gutman, Clayton Smith, Elizabeth Budde, Stephen J. Forman, Craig T. Jordan, Enkhtsetseg Purev CD123 CAR T cells for the treatment of myelodysplastic syndrome, Experimental Hematology 2019, doi: 10.1016/j.exphem.2019.05.002