TMOD-31. Patient-derived “tumor-oids” recapitulate the tumor microenvironment and allow for pre-clinical drug screening across the entire spectrum of pediatric brain tumors

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Abstract Traditional cell culture models are often infeasible and fail to adequately capture the tumor microenvironment of pediatric brain tumors. To address this gap, we developed a live bio-bank of patient-derived tumor-oids (PDTs) without single-cell dissociation to maintain the 3D architecture and microenvironment of pediatric brain tumors. Within multiple sites at the Children’s Brain Tumor Network (CBTN), we successfully established 125 PDTs from over 30 pediatric brain tumor types that underwent tumor resection, biopsy, or autopsy. The vast majority (96%) of PDTs from surgical resections demonstrated feasibility, defined as rounded viable organoids after 4 weeks, including previously difficult or impossible to culture low grade brain tumor types. Feasibility was optimized for: (1) tissue direct from OR, (2) storage in cold transport media for up to 48 hours, and (3) freeze/thaw with subsequent re-growth. Assessment of low-grade glioma PDTs demonstrated CD3 positive T cells in early passage PDTs (<4 weeks) and non-tumor neurons (MAP2+) and microglia (IBA1+) in late passage PDTs (4-8 weeks+). We performed personalized panel drug screens to rapidly identify tumor-specific drug sensitivities. To date, 15 PDTs have undergone individualized drug screens within 4 weeks of resection, revealing actionable vulnerabilities that correlated with molecular findings. In one case, a H3K27M-DMG PDT showed unique low nM sensitivity to selinexor; the patient was independently treated with selinexor for 12 months+ with ongoing remission. Ongoing work includes: (1) multi-omic comparisons of tumor tissue, early and late passage PDTs, and subsequent (tumor only) cell lines in DMG, CNS sarcoma, ependymoma and LGG/DNET models, and (2) integration of PDT-drug screen across homogenously treated target validation cohorts of patients in multi-site clinical trials (e.g. PNOC041). In summary, our work establishes the technical and biological feasibility of a precision medicine pipeline, allowing unprecedented access to living tumor tissue across the entire spectrum of pediatric brain tumors.

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