[Federal Register Volume 91, Number 161 (Friday, August 21, 2026)]
[Notices]
[Page 54338]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-17157]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government Owned Invention Available for License: Matched 
Patient-Derived 3D Isocitrate Dehydrogenase (IDH)-Mutant Glioma Cell 
Lines for Modeling Malignant Transformation

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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SUMMARY: 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: [email protected] 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.''
    NIH Reference Number: E-145-2026-0.
    Related Technologies: N/A.
    Product Type: Research Material/Tool.
    Therapeutic Area(s): Oncology [verbar] Neurology.
    Development Stage: Developed.
    Publications:
     Kim O, et al. A patient-derived cell model for malignant 
transformation in IDH-mutant glioma. (https://pubmed.ncbi.nlm.nih.gov/39256867/)
    Patents: PCT/US2024/054179, filed November 1,2024.
    Potential Commercial Applications:
     Molecular classification and diagnosis of CNS and kidney 
tumors, including difficult-to-classify and low-confidence cases.
     Diagnostic subtyping aligned to WHO-guided entities.
     Reference-lab and hospital-lab deployment.
     Clinical trial stratification and translational research 
cohort harmonization.
     Multi-classifier diagnostic decision support.
     Cancer treatment development.
    Competitive Advantages:
     Developed from a rigorously curated, large reference set 
of methylation profiles.
     Clinically relevant CNS diagnostic.
     CNS tumor methylation classes not represented in existing 
tools, expanding diagnostic coverage.
     Clinical-impact analysis creating superior diagnostic 
precision.
     Superior classifier for kidney cancer.
     Superior classifiers for multiple solid, difficult-to-
diagnose tumors.
     Integrative into clinical workflows, improving diagnostic 
practices and enhancing patient care.

    Dated: August 19, 2026.
Richard U. Rodriguez,
Associate Director, Technology Transfer Center, National Cancer 
Institute.
[FR Doc. 2026-17157 Filed 8-20-26; 8:45 am]
BILLING CODE 4167-05-P