Reona (Leo) Sakemura, M.D., Ph.D.
- Associate Consultant I, Department of Hematology Research
- Instructor of Medicine, Mayo Clinic College of Medicine and Science
What sparked your interest in individualized medicine?
My fascination with cancer therapy started at an early age. At 13, I was diagnosed with acute promyelocytic leukemia (APL) and underwent several courses of chemotherapies as well as a bone marrow transplant.
During the chemotherapy, I was lucky enough to receive the clinical trial of a novel drug called an all-trans retinoic acid (ATRA). An ATRA specifically targets the abnormal chromosome that leads patients to develop leukemia. It is now the standard care for treating a patient with APL.
The ATRA represents one of the first examples of individualized therapy targeted to leukemia. It has led to an improvement in cure rates from 30% to 90%.
What is your focus as a Gerstner Family Career Development Award recipient?
My life-changing early experience motivated me to become a hematologist. During my fellowship training in bone marrow transplantation, I devoted myself to patient care and invested in making myself a consummate clinician. During my fellowship, I fully turned my attention to immunotherapy — specifically to the concept that donor T cells can cure patients with relapsed or refractory malignancies. However, I also realized that not many patients with multiple myeloma could benefit from bone marrow transplants.
In 2013, I was accepted to the translational research program of the Nagoya University Graduate School of Medicine, where I completed a Ph.D. program. During this time, I started to work in the field of chimeric antigen receptor (CAR)-T cell therapy. CAR-T cell therapy has recently been applied to the treatment of a certain types of leukemia, lymphoma and multiple myeloma. The initial response of CAR-T cell therapies is high, but the durable response is not impressive. Many patients relapse after the treatment.
Other researchers and I speculate that the tumor microenvironment of multiple myeloma is inhibiting the anti-tumor activity of CAR-T cells. Therefore, we aim to target not only the cancer cells but also the tumor microenvironment with CAR-T cell treatment. Importantly, the safety profile of the novel CAR-T cell we are developing must be shown before it is tested in patients. We also are going to test the safety of the novel CAR-T cell in our humanized murine models. Finally, we will collect samples from multiple myeloma patients who undergo CAR-T cell therapy at Mayo Clinic to study CAR-T resistance mechanisms.
How will your research improve patient care?
The novel CAR-T cell therapy my team established in our laboratory overcame the negative impact of the tumor microenvironment and showed potent anti-tumor activity against multiple myeloma in the mouse models. Therefore, we speculate that our CAR-T cell therapy will improve the outcomes of patients with multiple myeloma. We will show the safety of our CAR-T cell in the humanized murine models. We also will define novel CAR-T resistance markers from patient samples.
How has the Gerstner Family Career Development Award helped advance your research?
I am grateful to the benefactors and selection committee for their generosity and support. This award has allowed me to continue focusing on this research. With this support, my team was able to establish the humanized multiple myeloma tumor microenvironment mouse model to study the efficacy and safety of our novel CAR-T cell therapy. This could not have been achieved without the generous support of this award.
Why did you choose Mayo Clinic to explore research?
Mayo Clinic research is extraordinary in both its breadth and depth. The research programs reflect the expertise, innovation and initiative of the faculty and staff worldwide. Most importantly, physicians and scientists from every medical specialty work in collaborative teams to advance discovery and translational research on behalf of patients. The combination of expertise and technology bolsters the innovations we make in our lab, driving promising research to effective practice.