Investigating the Potential of BH3 Mimetics and NK Cell Immunotherapy in Pediatric Sarcoma Treatment

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Rhabdomyosarcoma (RMS) is the primary soft tissue cancer in children, with poor survival rates despite improvements. To uncover improved treatment alternatives, in vitro models that accurately reflect the tumors are necessary. Therefore, we established a pipeline to develop primary patient-derived cells as new models for drug and immunotherapy testing. Preliminary results obtained in primary 2D monolayer and 3D spheroids show that RMS cells are sensitive to BCL XL and MCL-1 inhibitors, as well as to attack by activated allogenic NK cells. Killing by NK cells was further increased by expression of a B7H3-CAR construct. Additionally, these cells were validated for use in a patient-derived xenograft (PDX) model in vivo. To further build on these initial discoveries, we are currently performing larger drug screening approaches as well as mechanistic studies. Taken together, we aim to validate the use of primary cell-derived tumor spheroids as models of sarcoma and establish a platform for the development of novel therapeutics with combination of BH3 mimetis with NK cell-based immunotherapy. Publication History Article published online: 09 May 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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