Abstract
Murine models of human multiple myeloma (MM) are key tools for the study of disease biology as well as for investigation and selection of novel candidate therapeutics for clinical translation. In the last years, a variety of pre-clinical models have been generated to recapitulate a wide spectrum of biological features of MM. These systems range from spontaneous or transgenic models of murine MM, to subcutaneous or orthothopic xenografts of human MM cell lines in immune compromised animals, to platform allowing the engraftment of primary/bone marrow-dependent MM cells within a human bone marrow milieu to fully recapitulate human disease. Selecting the right model for specific pre-clinical research is essential for the successful completion of investigation. We here review recent and most known pre-clinical murine, transgenic and humanized models of MM, focusing on major advantages and/or weaknesses in the light of different research aims.
Highlights
Multiple myeloma (MM) is characterized by the expansion of malignant plasma-cells (PCs) within a permissive bone marrow microenvironment (BMM) that promotes tumor cell survival and proliferation [1]
The transition from monoclonal gammopathy of undetermined significance (MGUS) to MM takes place by progressive mutational events accompanied by changes in the BMM [3, 4]
Most of preclinical findings in MM research that translated into clinics as effective therapies have been developed by the use of a variety of in vivo models, which aim to recapitulate the disease and to provide insights on the interactions between MM cells and the surrounding microenvironment
Summary
Multiple myeloma (MM) is characterized by the expansion of malignant plasma-cells (PCs) within a permissive bone marrow microenvironment (BMM) that promotes tumor cell survival and proliferation [1]. This mouse (MITRG) allowed easier engraftment of human hematopoietic cells derived from peripheral blood or BM [81] and development of innate immune system cells (Figure 1) The latter is a very relevant feature of this model as human innate immune system plays a prominent role in the study of tumor growth in the context of chronic inflammatory stimuli. The discovery of immune checkpoints and the rapid development of inhibitory monoclonal antibodies to these molecules raised the question on the best suitable model to choose for the study of new immune-modulatory agents In this view, several immunocompetent mouse models of MM, including the 5TMM and vk*MYC, have been widely used to investigate the role of different immunosuppressive cell populations and the activity of checkpoints inhibitors such as anti-PD1 mAbs [90,91,92,93,94,95]. The SCID-hu and the SCID-synth-hu represent a strong improvement in this direction, especially taking into account that immune populations, such as dendritic cells, have been reported to be present and functionally active in the latter model [97]
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