Elucidating Mechanisms of CAR-T Cell Immunotherapy Resistance and Sensitivity to Improve Treatment of Myeloma
Abstract
Scientific Objective and Rationale: Multiple myeloma is a type of blood cancer that affects plasma cells and is generally incurable. In multiple myeloma, malignant plasma cells accumulate in the bone marrow and crowd out normal tissue, which can lead to impaired immune function, bone loss, and kidney damage. Conventional cancer treatments, such as chemotherapy, are effective against multiple myeloma in the short-term, but can lower quality of life due to side effects and need to change frequently when tumors become insensitive. New approaches to treating cancer include the use of immune therapies, which train a patient’s immune system to fight cancer. There has been remarkable success using immune therapies to treat multiple myeloma as evidenced by the U.S. Food and Drug Administration’s recent approval of two types of chimeric-antigen-receptor (CAR) T cell therapies. One drawback to CAR-T cell therapy, which seems to be unique to treating multiple myeloma, is that while it is highly effective and safe, nearly all patients relapse on average 1 year post treatment. Our research will focus on understanding (i) biological phenomena underpinning this lack of more durable cancer control by CAR-T therapy, and (ii) test an alternative way of creating CAR-T therapy from immune cells that we hypothesize could be more effective specifically in the fight against multiple myeloma. To achieve these goals, we will employ the internationally recognized and clinically faithful mouse model of multiple myeloma for controlled experimentation. Our overall goal is to improve upon the highly effective immune therapies for multiple myeloma, with a vision for a future where safe, effective, durable treatment that utilizes a patient’s own immune system can be employed early in the disease and may ultimately eliminate multiple myeloma. Career Goals in Cancer Research: Dr. Meermeier aspires to be a leader in understanding how to use the immune system to fight multiple myeloma and other cancers. She is a Ph.D.-trained research immunologist who enjoys collaborating on multidisciplinary teams with physicians and basic scientists, who aims to translate her discoveries in the laboratory into new treatments for patients with multiple myeloma. This award will expand Dr. Meermeier’s research program, foster new collaborations and projects, and allow her to pursue an ambitious set of experiments that could identify ways to advance immune therapies for multiple myeloma in the future. Dr. Meermeier will interact regularly with Drs. Bergsagel, M.D. and Chesi, Ph.D., world renowned myeloma specialists to ensure career and research milestones are accomplished. Applicability of the Proposed Research: Overall, successful completion of this translational project may help many patients with multiple myeloma by identifying ways to make immune therapy more durable by subverting drug resistance. We hope that, by the end of the award period, the research will provide the rationale for further CAR-T cell development and correlative studies in multiple myeloma patients undergoing CAR-T therapy. We anticipate that this research will contribute to engineering next-generation CAR-T cell therapy more tailored to fight multiple myeloma and inform possible combinations of existing immune therapies that could give patients much longer periods of cancer-free life. Overarching Challenge: In this proposal we aim to advance immunotherapy, specifically for multiple myeloma but also in ways that may apply to other cancers in the future. We expect our investigations will advance our understanding of CAR-T treatment resistance and recurrence that develops often in patients with multiple myeloma. If successful, we expect our findings will contribute to making CAR-T cell therapy more effective and applicable to more patients, in time, reducing the need for conventional chemotherapies with more substantial treatment side effects. Relevance to Military Health: Give
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310298
Entities
People
- Erin Meermeier
Organizations
- Mayo Clinic Scottsdale
- United States Army