Government Owned Invention Available for License: Matched Patient-Derived 3D Isocitrate Dehydrogenase (IDH)-Mutant Glioma Cell Lines for Modeling Malignant Transformation
The National Cancer Institute (NCI) seeks licensees for matched patient-derived 3D Isocitrate Dehydrogenase (IDH)-mutant glioma cell lines, 403L and 403H, generated from the sam...
The National Cancer Institute (NCI) seeks licensees for matched patient-derived 3D Isocitrate Dehydrogenase (IDH)-mutant glioma cell lines, 403L and 403H, generated from the same patient before and after malignant transformation from WHO grade 2 to WHO grade 4 disease. This research material provides an opportunity to study IDH-mutant glioma progression, temozolomide-associated hypermutation, invasion, metabolism, and treatment resistance.
FOR FURTHER INFORMATION CONTACT:
Inquiries related to this license opportunity should be directed to: Michael Pollack, Unit Supervisor, NCI, Technology Transfer Center, Email:
michael.pollack@nih.gov
or Phone: 240-276-5519.
SUPPLEMENTARY INFORMATION:
IDH-mutant gliomas often begin as lower-grade tumors but remain incurable and frequently progress to higher-grade disease through malignant transformation. This is clinically important but difficult to study because matched low-grade and high-grade tumor materials from the same patient are rare. Further, fixed tumor specimens are limited for repeated mechanistic or drug-response experiments.
Researchers at the NCI developed a matched pair of patient-derived cell models, 403L and 403H, from the same patient before and after malignant transformation. 403L was established from a WHO grade 2 IDH-mutant astrocytoma. 403H was derived from the recurrent WHO grade 4 tumor following radiation and temozolomide treatment. Both cell lines: (1) grow as 3D spheroids, (2) retain endogenous IDH1 R132H expression, and (3) were authenticated to the patient's germline by short tandem repeat (STR) profiling (100% match for 403L; 93.33% match for 403H).
The high-grade 403H line shows increased invasive behavior, temozolomide-associated hypermutation (tumor mutational burden of 70.07/Mb vs. 3.96/Mb in 403L), upregulated epithelial-mesenchymal transition (EMT) signaling (whereas Notch signaling is enriched in 403L), and changes in glioma-associated metabolism, including 2-hydroxyglutarate (2-HG), glutamine, fatty acid metabolism, and lactate/pyruvate flux. Furthermore, 403H showed significantly greater 3D invasion than 403L (p<0.0001). 403H formed infiltrative high-grade glioma in 4 of 5 orthotopically xenografted NSG mice. In contrast, 403L did not form tumors within 18 months.
“This Notice is in accordance with 37 CFR 404.4 Authority to grant licenses.”
37 CFR 404.4
pubmed.ncbi.nlm.nih.gov/39256867/