Abstract 3918: Development and validation of a systemic human multiple myeloma model utilizing luciferase expressing H929 tumor cells

Abstract Multiple Myeloma (MM) is the second most common hematological malignancy of clonal plasma cells that originates in the bone marrow (BM). Despite significant advancements in the treatment of MM, this disease remains incurable with a poor prognosis in relapsed/refractory patients. MM has complex disease dynamics due to the genetically diverse clonal population of myeloma cells. Thus, pre-clinical models are needed to translate tumor heterogeneity for appropriate risk assessment and the development of safe and effective treatment regimens. We established a Multiple Myeloma in vivo model by systemic implantation of the luciferase-expressing tumor cell line H929 (H929-luc) into immunodeficient NCG mice. First, we generated a H929-luc monoclonal cell line from a polyclonal pool of stable luciferase-expressing cells by limiting dilution cloning. Single cells from the stable pool were expanded in selection medium and based on in vitro growth properties and bioluminescence intensity H929-luc monoclonal lines were selected for in vivo evaluation. The in vivo tumor growth profile was determined by testing the monoclonal lines at two different cell inoculums, and disease progression was monitored by in vivo serial bioimaging. For validation of the H929-luc in vivo model, we determined the efficacy and survival benefit in response to various clinically relevant standard of care agents including dexamethasone, daratumumab, cyclophosphamide, and vincristine. The quantification of tumor burden by bioluminescent imaging showed reduced tumor burden and prolonged survival with cyclophosphamide and vincristine. Taken together, we have developed a well characterized and robust systemic H929-luc model that recapitulates the disease dissemination and invasiveness of multiple myeloma for evaluating novel therapeutic approaches to treatment. Citation Format: Bincy John, David Harris, Shu-Chuan Chou, Tyler Rowe, Nicole Westrick, Nick Nightenhelser, Andrew Wong, Elizabeth Rainbolt, Zachary Ward, Jessica Neil. Development and validation of a systemic human multiple myeloma model utilizing luciferase expressing H929 tumor 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 3918.