Immune effector cell therapies in multiple myeloma

• Applicant: Dr. Midas Seyda
• Subject Area: Hematology, Oncology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516161452

Multiple myeloma (MM) is a malignant clonal plasma cell disease and accounts to the second most common hematological malignancy. Despite development of immunotherapies including immune effector cell treatments during the last decade, MM is still considered an incurable disease. Extramedullary disease disease (EMD) remains a major obstacle to achieving long-term remission in MM including immune effector cell therapies such as chimeric antigen receptor (CAR) T cells. We propose that MM cells specifically in EMD render the CAR T cell immunosurveillance ineffective. Elucidating the underlying mechanisms may therefore be critical in understanding CAR T cell-refractory outcomes and help create precise and spatial-adjusted treatment regimens. The proposed project intends to (1) gain an understanding of the differences between bone marrow and EMD sites that contribute to lack of CAR T cell responsiveness and a proclivity for relapse in extra-osseous sites of hematologic malignancies; and (2) to investigate if CAR engineering approaches can overcome spatial changes that contribute to immune escape and the immunosuppressive TME in MM, thereby generating an armored CAR T cell approach tailored for EMD. Ultimately, we anticipate that in the future, as Prof. Smith has demonstrated before, these pre-clinical studies may be translated to advance immune effector cell therapies in the clinic.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Eric Smith, Ph.D.