Combined cytotoxic and immune-stimulatory gene therapy for glioma

Yoshie Umemura and colleagues conducted a dose-finding, first-in-human clinical trial to investigate the safety and activity of the combined therapy of HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with newly diagnosed high-grade glioma. 1 Umemura Y Orringer D Junck L et al. Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. Lancet Oncol. 2023; 24: 1042-1052 Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar The discoveries offer innovative therapeutic approaches for high-grade glioma, with the potential to enhance overall survival without significant adverse events. Furthermore, they shed light on the characteristics of the tumour immune microenvironment. Nevertheless, there are certain recommendations to consider moving forward. Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trialThe combination of two adenoviral vectors demonstrated safety and feasibility in patients with high-grade glioma and warrants further investigation in a phase 1b/2 clinical trial. Full-Text PDF Combined cytotoxic and immune-stimulatory gene therapy for glioma – Authors' replyThe letter by Binghao Zhao and colleagues accurately describes the main findings of our phase 1 trial of the combined adenoviral therapy using HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with newly diagnosed high-grade glioma.1 In our dose-finding, first-in-human clinical trial, we established the safety and biological activity of this treatment. The trial established the highest dose tested (ie, 1 × 1011 viral particles of each of the two vectors) as the dose that can be used in follow-up clinical trials, as the maximum tolerated dose was not reached. Full-Text PDF