Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors

“…Such per-operative administrations are already carried out during surgery delivering local chemo-or gene-therapies to GBM patients. 37 Supporting this possibility, this study unambiguously shows that a significant fraction of Vg9Vd2 T cells survive for several days following a stereotaxic injection into the mouse brain parenchyma and subsequently deeply infiltrate brain tissue. Both in vitro and in vivo assays were carried out with dose-dependent zoledronate sensitizations of a GBM cell line and primary human GBM cells in order to trigger strong Vg9Vd2 T cell recognition, as already used for enhancing such reactivities in other oncological contexts.…”

A systematic review and meta‐analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

“…This is exemplified by two unsuccessful phase III randomized controlled trials of gene therapy16, 17 and variable responses in other smaller clinical studies 6, 18, 19, 20, 21…”

Potential new gene therapy option with sitimagene ceradenovec for newly diagnosed patients with glioblastoma multiforme

“…7 However, no statistically significant difference in overall survival was reported (sitimagene ceradenovec, 497 d vs standard care 452 d; hazard ratio [HR] 1.18, 95% CI 0.86-1.61; P = 0.31). O 6 -alkylguanine DNA alkyltransferase (MGMT) status in patients with glioblastoma increasingly is becoming of greater clinical significance as it can help guide chemotherapeutic regimens.…”

“…10 In a subgroup analysis of patients that expressed MGMT in tumors within the experimental group, sitimagene ceravendoc was found to have a greater effect on the primary endpoint of the study compared with the whole cohort (HR 1.72, 95% CI 1.15-2.56, P = 0.008). 7 The study also evaluated the effect of anti-adenoviral neutralizing antibodies as this could compromise efficacy of sitimagene ceradenovec. At baseline screening of patients, 46 patients in the experimental group and 37 patients in the control group had quantifiable anti-adenoviral antibody levels.…”

“…One of these included use of a re-intervention committee, which was masked to treatment, to minimize bias. 7 The committee found that when reintervention was called for, no bias was detected among the whole cohort. The authors also disclosed conflict of interests, including 4 of the 9 authors had a vested interest in sitimagene ceradenovec, either through direct employment for Ark therapeutics or as shareholders in the company.…”