TMOD-09. Construction of experimental models of spinal cord glioma based on clinical samples

Spinal cord gliomas are malignant intramedullary tumors with lower incidence compared to brain gliomas, predominating in adolescents and exhibiting distinct molecular genetic profiles. Notably, treatment options for spinal cord diffuse midline gliomas with H3 K27 alteration (H3-SCDMG) are extremely limited, as conventional therapies (surgery, radiotherapy, chemotherapy) yield suboptimal efficacy. Developing novel therapeutic strategies is thus an urgent need in neuro-oncology. However, the scarcity of disease incidence and lack of suitable preclinical models hinder research. Establishing representative animal and cellular models is therefore critical for studying H3-SCDMG biology and evaluating treatments.This study employed patient-derived xenograft (PDX) methodology, engrafting fresh H3-SCDMG tumor tissues into immunodeficient mice to generate PDX models. Patient-derived cell lines (PDCs) were concurrently established via tumor tissue dissociation and culture. Whole-exome sequencing (WES), immunohistochemistry (IHC), and immunofluorescence (IF) confirmed the histological and molecular genetic fidelity of both PDX tissues and PDCs to the original patient tumors.The successfully established H3-SCDMG PDC model was utilized for in vitro drug sensitivity screening. Key findings were subsequently validated in vivo using both subcutaneous and orthotopic spinal cord PDX models.We have successfully developed biologically faithful PDX and PDC models of H3-SCDMG that recapitulate patient tumor growth. These models provide ample biological material for clinical therapeutic research, accelerating H3-SCDMG investigation and facilitating improved patient outcomes.