Suzanne Lentzsch, MD, PhD, Wade F. B. Thompson CLIP Investigator Columbia University Medical Center Area of Research: Multiple Myeloma Multiple myeloma (MM) is complicated in more than 80% of patients by devastating bone disease that barely repairs after disease remission. Current agents for bone disease management including bisphosphonates only partially inhibit the progression of bone lesions and can cause severe side effects including acute renal failure, albuminuria, and osteonecrosis of the jaw. In addition, the severely compromised immune system in myeloma patients results in the incapability of immune cells to control myeloma cells and infectious pathogens. Unfortunately, checkpoint inhibitor drugs against PD-1 and PD-L1, which have revolutionized the treatment of various solid tumors, failed in myeloma treatment. In addition, a biological connection between bone disease and impairment of the immune system in MM has not been identified. Dr. Lentzsch’s studies, for the first time, reveal that matrix metalloproteinase 13 (MMP-13) is highly expressed by myeloma cells and triggers both bone disease and immunosuppression. She will demonstrate that checkpoint protein PD-1H/VISTA is the specific receptor for MMP-13 and mediates MMP-13 induced bone disease and immune suppression. Thereby, she presents MMP-13/PD-1H axis as a novel module that links bone disease, immune suppression, and subsequently tumor progression in MM. This proposed study will validate the in vivo role of MMP-13/PD-1H axis as a therapeutic target for MM bone disease and immune regulation using comprehensive animal models and myeloma patient biopsies. Dr. Lentzsch posits that therapies targeting the MMP-13/PD-1H axis may represent promising novel treatments to manage bone disease and immune dysfunction and eventually conquer this incurable disease. Projects and Grants Checkpoint Inhibitor PD-1H (VISTA) Links Multiple Myeloma Bone Disease and Myeloma Induced Immunosuppression Columbia University Medical Center | Multiple Myeloma | 2020
