Personalized tumor-derived dendritic cell therapy to overcome residual disease in multiple myeloma

Multiple Myeloma (MM) is the second most common hematological cancer, characterized by the malignant transformation of plasma cells within the bone marrow niche. Despite therapeutic advances, MM remains incurable for the majority of patients. Dendritic cells (DC) are ‘sentinels’ of the immune system endowed with the mission to recognize pathogens and cancer cells, and alert effector cells to combat the invaders. The DC population represents a heterogeneous mixture of distinct subsets including plasmacytoid DCs (pDCs) and
conventional DCs (cDCs); further subdivided in cDC1 and cDC2. Each subset differs in its capacity for antigen uptake, processing and T cell activation. In MM, ex vivo generated monocyte-derived DCs used for therapy were well tolerated in patients, but did not result in long-term clinical responses. Previous studies in cancer highlighted the importance of cDC1 and cDC2 vaccination to boost a potent anti-tumor immune response. Therefore, in this project, I aim to (1) thoroughly characterize and unravel the role of cDC subpopulations in MM and (2) evaluate the immune and anti-tumor effects of DC-boosting strategies in vivo. On the short term, this project will improve our understanding on the role of cDC subsets in MM, and will provide novel insights on the impact of DC boosting strategies on DC number, phenotype and anti-tumor potential. On the long term, this knowledge will contribute to the design of a new cDC-based vaccination approach as a therapeutic intervention in MM. The proposed project promises to yield further insights in the use of DC-based immunotherapy as a treatment option for MM patients.