Matteo Maria Bellone, MD, CRI CLIP Investigator Vita-Salute San Raffaele University Area of Research: Multiple Myeloma Multiple myeloma (MM) is an incurable medical condition where abnormal plasma cells in the bone marrow (BM) multiply uncontrollably causing BM dysfunction. MM is preceded by a “precancerous” stage referred to as asymptomatic smoldering MM (SMM) where patients can remain asymptomatic but are at a higher risk of active MM over time. SMM patients are often only offered observation rather than any active treatment leading to their frustration and anxiety. Dr. Bellone developed a genetic mouse model of MM where they showed a direct link between gut microbiota and a population of T cells that produce interleukin-17 (T helper 17 or Th17 cells). Th17 cells migrate to the BM during the asymptomatic phase of the disease and favor expansion of abnormal plasma cells, thus fueling progression from SMM to symptomatic MM. Furthermore, higher levels of IL-17 in bone marrow of SMM patients is known to be predictive of disease progression. Data generated by Dr. Bellone indicated that in asymptomatic animals, modulation of gut microbiota by administration of a specific bacterial species, called Prevotella melaninogenica, controlled expansion of Th17 cells and delayed progression to symptomatic disease. Their data also showed that Prevotella melaninogenica synergized with immune checkpoint blockade therapies, finding that has significant clinical implications for using combinatorial therapeutic approach even in the asymptomatic disease phase. Dr. Bellone’s research has significant scientific, social, and economical impact. In 2022 alone, there were 34,470 new cases of MM and 12,640 MM related deaths in the US. These numbers are expected to rise in the years to come due to the aging population. Early treatment of SMM patients is therefore a much-needed pursuit that can lead to better patient outcomes and reduce unnecessary suffering. Dr. Bellone aims to use CRI’s CLIP funding to fully exploit the potentials of their preliminary findings and provide proof of principle of a novel therapeutic strategy for SMM patients, which is based on administration of a probiotic and could be applied with various combination therapies leveraging gut microbiota-mediated modulation of the immune system. Projects and Grants Switching multiple myeloma trajectory by dual modulation of gut microbiota and immunity Vita-Salute San Raffaele | Multiple Myeloma | 2023
