Invention Novelty: A stable, patient-derived IDH- 1 mutant glioma xenograft designed to evaluate potential IDH targeted drug therapies.
Value Proposition: IDH-1 (Isocitrate Dehydrogenase) is a very common mutation observed in low-grade glioma tumors. Current IDH-mutated cell lines lack sufficient genetic characteristics similar to human pathologies and restrict discovery of effective targeted therapies. This invention is an IDH-1 mutant glioma model derived from patient tissue called JHH273 and meets a critical need to test drug agents targeting mechanisms involved in glial tumor formation. Other advantages include:
• Maintains IDH-1 mutation features observed in human primary glial brain tumors
• Models demonstrate in vivo therapeutic response to drugs targeted at IDH mutations
• Further knowledge of cellular mechanisms induced by IDH oncogenes
Technical Details: Johns Hopkins researchers have developed an in vivo IDH-1 glioma mouse xenograft model to further study effective therapies for IDH mutations characterized by increased DNA methylation and production of the common oncometabolite, 2-HG. Difficult grafting cell-culture techniques and current engineered cell line quality have limited additional laboratory studies; however, this model was developed directly from a WHO grade III- glial cell positive cancer patient with a confirmed IDH mutation through DNA sequencing. Additionally, when models were exposed to a demethlyating agent, 5-azacytidine, a reduction in methylation and tumor growth was observed opening the door for more clinical analysis.
Publication(s)/: Oncotarget, 4(10), 1737-1747
