Abstract 1282: Development of a humanized multiple myeloma mouse model using bone-derived MM.1S cells

Abstract Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. The symptoms of MM patients include e.g. bone lesions, renal dysfunction, and anaemia. While advancements in treatment have improved outcomes for many patients, MM remains largely incurable. The development of preclinical models is crucial as they provide information on drug efficacy and mechanisms of action. 5 x 106 MM.1S cells tagged with GFP and luciferase (BPS Bioscience) were inoculated intravenously to NSG-Tg(huIL-15) mice (The Jackson Laboratory) and harvested for further in vitro cell culture at day 77. 20 x 106 cells of parental or bone-derived MM.1S cells were later inoculated intravenously to NSG-Tg(huIL-15) mice for comparison of the growth rate. Tumor growth was followed by weekly bioluminescence imaging. In vivo micro-CT imaging of the left tibia was performed in each group for evaluation of the bone lesions when the first mouse was sacrificed, at day 35 in the study group with bone-derived cells and at day 60 in the study group with parental cells. The animals with bone-derived cells were euthanized within study days 35-40 based on humane end point criteria. The study groups with parental cells were sacrificed at study day 73, when most mice were at humane end point. The bioluminescence signal was detected in skeletal sites (spine, pelvis, hind limbs, calvaria, ribs) and in soft tissues (spleen, brain, lungs, ovaries). Extensive osteolytic lesions were observed in all mice that had received the bone-derived cells, compared to 40% in the parental cell group. The bone-derived cell line was further characterized for cell surface marker expression. Both parental and bone-derived cells are positive for BCMA, CD138, and SLAMF7, which can be used for tumour cell identification in bone marrow. We conclude that the bone-derived MM cells induce disease progression in this mouse model with shorter study length compared to the parental cell line and that both cell lines express BCMA, CD138, and SLAMF7. The interaction between myeloma cells and their surrounding microenvironment in bone marrow plays a critical role in MM. The bone-derived MM.1S model can be combined with human NK cells or peripheral blood mononucleic cells (PBMCs) to study therapeutics affecting the interaction of cancer and immune cells. Citation Format: Mari I. Suominen, Katja M. Fagerlund, Mervi Ristola, Justyna Zdrojewska, Yumei Diao, Kristina Witt-Mulder, Stefan Svensson Gelius, Jukka P. Rissanen, Jenni H. Mäki-Jouppila. Development of a humanized multiple myeloma mouse model using bone-derived MM.1S cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1282.