Abstract 4196: Successful establishment of human rhabdomyosarcoma xenografts in a human-adapted mouse model

Abstract

Abstract Purpose: The outcome of patients with advanced stage rhabdomyosarcoma is still sobering. Treatment results cannot be improved by conservative treatment options. Therefore, novel treatment approaches such as immunotherapy need to be evaluated in human-adapted animal models. The aim of this study was to develop a humanized mouse model of childhood rhabdomyosarcoma as a basis for studies of immunotherapeutic approaches. Methods: NOD/LtSz-scid IL2R gamma null mice were used for all experiments (n =14). Animals underwent subletal irradiation (1 × 300cGy). Afterwards, transplantation of human CD34+-cells (1.000.000 cells per animal i.v.) was carried out. Eight weeks after transplantation, subcutaneous xenotransplantation of human alveolar (Rh30) and embryonal rhabdomyosarcoma (RD) cell lines was carried out. Engraftment of human cells was assessed in peripheral blood at day 21 and at day 55 of the experiment. Animals were sacrified and tumors were resected 93 days after CD34+-transplantation. Results: Successful engraftment of human cells with establishment of a human immune system was observed in 12 of 14 animals. B-cells and T-cells were mostly detected in the peripheral blood. There were only a few monocytes and nearly no NK-cells. Xenotransplantation of alveolar RMS resulting in subcutaneous tumor growth was feasible in 7 animals. Xenotransplantation of embryonal RMS was performed in 5 animals and led to tumor growth in 1 animal. Histological work up showed either alveolar or embryonal RMS cells with central necrosis. Conclusion: For the first time, we developed a xenotransplantation model of human rhabdomyosarcoma in a humanized mouse model. Establishment of subcutaneous tumor xenografts was more effective in alveolar subtype. This model will serve as basic research tool for further analysis of novel immunotherapeutic approaches in solid pediatric tumors. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4196.