Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges, Opportunities, and Future Directions

Abstract

Immunotherapeutic approaches, including adoptive cell therapy, revolutionized treatment in multiple myeloma (MM). As dendritic cells (DCs) are professional antigen-presenting cells and key initiators of tumor-specific immune responses, DC-based immunotherapy represents an attractive therapeutic approach in cancer. The past years, various DC-based approaches, using particularly ex-vivo-generated monocyte-derived DCs, have been tested in preclinical and clinical MM studies. However, long-term and durable responses in MM patients were limited, potentially attributed to the source of monocyte-derived DCs and the immunosuppressive bone marrow microenvironment. In this review, we briefly summarize the DC development in the bone marrow niche and the phenotypical and functional characteristics of the major DC subsets. We address the known DC deficiencies in MM and give an overview of the DC-based vaccination protocols that were tested in MM patients. Lastly, we also provide strategies to improve the efficacy of DC vaccines using new, improved DC-based approaches and combination therapies for MM patients.

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

“…However, over the last decades several DC vaccine formulations with sufficiently wide spectrum of immunogenicity have been clinically tested without sufficiently proportional clinical success. 101 , 251–255 Thus, it is not clear if the lack of immunogenicity is the sole reason for clinical failure of DC vaccines or if there are also specific primary, adaptive, or acquired resistance pathways that require better attention, together with the limitations of preclinical models in accurately reflecting the clinical reality. 256–259 We believe that preclinical research needs to better address the previous clinical failures of DC vaccines and move forward in a definitive fashion to avoid redundancy.…”

Calreticulin as an Adjuvant In Vivo to Promote Dendritic Cell Maturation and Enhance Antigen-Specific T Lymphocyte Responses against Melanoma

“…DC-based cancer vaccines are based on optimal antigen presentation and T cell activation of DCs. Between 1995 and 2021, many DC vaccines were tested in melanoma, B cell lymphoma, metastatic colorectal cancer, hematologic malignancies, and hepatocellular cancer [27][28][29][30][31]. A critical area in DC vaccine design and translation is the culture condition.…”

Different Roles of Dendritic Cells for Chronic Rhinosinusitis Treatment According to Phenotype

“…Mouse cDC2 is specifically used for MHC II presentation and the induction of CD4 + T cell responses, including Th1, Th2, and Th17 cells [ 21 ]. Compared to mouse cDC1, which mainly initiates the cellular immune response, mouse cDC2 mainly initiates the humoral immune response [ 22 ].…”