Oncolytic Effect of Adenoviruses Serotypes 5 and 6 Against U87 Glioblastoma Cancer Stem Cells

Abstract

Background/Aim: Oncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells. Materials and Methods: Oncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively. Results: Ad6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group. Conclusion: Ad6 was shown to be a promising agent for treating glioblastomas.

Palliative Radiotherapy of Primary Glioblastoma

“…Since the majority of patients with glioblastoma have poor prognoses, a considerable number of pre-clinical studies were performed during recent years to better understand this aggressive disease and contribute to the improvement of its treatment (12)(13)(14)(15)(16)(17). Another strategy to improve the outcomes of glioblastoma patients is personalization of their treatment.…”

Re-Irradiation for Recurrent Glioblastoma Multiforme

“…GBM is the most common primary brain tumor in adults and is often associated with a poor prognosis (1-3). Despite the introduction of multi-modality treatment approaches and considerable pre-clinical and clinical research, the prognoses of patients with GBM need to be improved (4,5,(15)(16)(17). The poor prognoses are mainly the consequence of intracerebral recurrences.…”

Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy

“…The wild-type Ad6 vector has been shown to exhibit a strong dose-dependent cytotoxicity against glioblastoma in vitro models. The administration of Ad6 into U87MG subcutaneous xenografts resulted in a significant therapeutic effect, which was comparable to that with Ad5 wild-type control [89]. In addition to tumor size, the ability of Ad6 to destroy the stem cells in glioblastoma tumors has been assessed.…”