Combination of BH3 mimetics with NK cell-based immunotherapy as a potential novel treatment option for pediatric sarcoma

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Rhabdomyosarcoma (RMS) is the most prevalent malignant soft tissue cancer in children. Despite intensive therapy regimens, survival rates are low, and better treatment options are urgently required. To discover improved treatment alternatives, in vitro models accurately reflecting tumor biology are necessary. Therefore, we established a pipeline to develop primary patient-derived cells as new models for pre-clinical drug and immunotherapy testing. As proof of concept, we tested allogenic Natural Killer (NK) cell attack and BH3-mimetics in primary 3D spheroids (n=6) as well as 2D cultures. Initial results show that RMS are sensitive to NK cell attack as well as selective BH3-mimetics targeting BCL-XL. To further expand these findings, we are optimizing culture conditions to perform large-scale drug screening approaches as well as mechanistic studies in RMS. Taken together, we validated the use of primary cell-derived tumor spheroids as models of sarcoma and established a platform for the development of novel therapeutics. Publication History Article published online: 10 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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