Details

Autor(en) / Beteiligte

• Shukla, Nikhil
• Davis, Harold
• Vallabhapurapu, Subrahmanya
• Qi, Xiaoyang

Titel

EXTH-65. AS1411 ENHANCES CYTOTOXICITY OF SapC-DOPS VIA SURFACE PHOSPHATIDYLSERINE ELEVATION IN GLIOBLASTOMA

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2017-11, Vol.19 (suppl_6), p.vi87-vi87

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2017

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Glioblastoma multiforme (GBM) remains a common and deadly primary brain tumor. Current treatment includes surgical resection with adjuvant chemotherapy and radiotherapy. However, median survival remains less than 15 months mainly due to tumor recurrence and drug resistance. SapC-DOPS, also called BXQ-350, is a stable protein-lipid nanovesicle that has been shown to have anti-GBM activity and is now in a Phase 1 clinical trial. SapC-DOPS selectively targets phosphatidylserine (PS) which is abnormally exposed on the cancer cell surface. It is known that the antitumor efficacy of SapC-DOPS is correlated with the level of surface PS on GBM cells. AS1411, a stable G-rich DNA oligo and the first aptamer to progress to clinical trials, has anticancer activity via a methuosis-induction pathway. The aptamer predominantly functions via nucleolin binding in tumor cells. However, methuosis-induced cell death by AS1411 in GBM cells has not previously been described. Our morphologic analyses of U87-MG cells treated with AS1411 showed vacuolization similar to the known methuosis inducer, MIPP. Utilizing flow-cytometry we demonstrated that treatment of U87-MG cells with AS1411 induced a time-dependent increase in surface PS, with greater than 2-fold increase in surface PS at the 72-hour time point (p < 0.005). Interestingly, AS1411 mediated increase in surface PS resulted in enhanced response to SapC-DOPS. Combination treatment with various concentrations of SapC-DOPS and AS1411 showed increased antitumor effects against U87-MG cells (p < 0.01). Our study elucidates a potential role of AS1411 in sensitizing GBM to SapC-DOPS through surface PS elevation. This combination therapy may provide a new clinical modality for treating GBM patients.