Combination Treatment for Glioblastoma Cells with Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Oncolytic Adenovirus Delta-24

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits cancer-selective killing activity representing a promising anticancer therapeutic strategy. Adenovirus Delta-24 is another interested anticancer agent selectively killing cells with a defective p16/Rb/E2F pathway. However, many types of cancer, including gliomas, could develop resistance to Delta-24 or TRAIL-induced apoptosis. In this study, we investigated whether TRAIL, in combination with adenovirus Delta-24, could result in an enhanced antiglioma effect in vitro in a panel of glioblastoma cell lines (U87MG, U251MG, D54, and T98G). The treatment of glioblastoma cell lines with TRAIL and Delta-24 adenovirus in combination showed markedly enhanced effect, compared to each agent alone.

Targeting Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL): A Promising Therapeutic Strategy in Gliomas

“…Adenoviral infection causes cell death, apart from autophagy, through apoptotic pathways by activation of caspase 8. 11 Treatment of glioblastoma cells with TRAIL and Delta-24 adenovirus in combination showed a markedly enhanced effect when compared with each agent alone. 11 …”

“…D54 cells are sensitive to TRAIL and resistant to U251MG, whereas T98G and U87MG display moderate sensitivity. 11 Figure The extrinsic and intrinsic pathway of apoptosis. In the extracellular pathway, TRAIL forms trimers that recognize and bind to their cognate death receptors, which in turn leads to the recruitment of the adapter FADD.…”

Targeting glioblastoma with oncolytic adenovirus delta 24

“…Treatment to glioma with Ad-Δ24 or its derivatives has been observed to enhance when combined with TRAIL, [16] adenovirus expressing p53, [22] temozolomide, [23] radiation [24] and topoisomerase I inhibitor irinotecan. [25] Autophagic induced cell death and induction of apoptosis are well-characterized results of Ad-Δ24 infection giving the erratum for combination treatments.…”

“…[13] But despite its potent antiglioma effect, it was obvious even from the first studies that Ad-Δ24 would need further improvements for optimal therapeutic effect. [16] ADENOVIRUS DELTA 24 DERIVATIVES A significant number of modifications have been applied on the initial Ad-Δ24 system trying to enhance its specific targeting or to augment its oncolytic potency. The most important effort that has been made to enhance glioma targeting was the insertion of an Arg-Gly-Asp peptide (RGD) in the Ad-Δ24 fiber knob, increasing its affinity with integrins that are highly expressed in gliomas and other tumor cells.…”

Human enteroviruses exhibit selective oncolytic activity in the model of human glioblastoma multiforme xenografts in immunodeficient mice

“…Members of various virus families are used to design oncolytic viruses to treat human gliomas. Among these are herpes viruses, Newcastle Disease virus [7][8][9][10][11], adenoviruses [12][13][14][15][16], parvoviruses [17][18][19], reoviruses [20][21][22][23] , enteroviruses [24][25][26][27] etc [1]. Numerous clinical trials have shown that oncolytic virus preparations are non-toxic [28][29][30][31].…”