Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma

Summary

Despite the marginal improvements in survival of patients suffering from malignant glioma treated with gene therapy vectors, the clinical trials conducted so far using viral vectors, in particular adenoviral vectors, have proven that the use of adenoviral vectors is a safe therapeutic approach, even in large, multicenter, phase 3 clinical trials. Treatment of malignant glioma using gene transfer modalities typically consists of surgical debulking of the tumor mass followed by the administration of the viral vectors into the brain tissue surrounding the tumor cavity. This study will combine direct tumor cell killing (TK) and immune-mediated stimulatory (Flt3L) gene transfer approaches delivered by first generation adenoviral vectors.

Timeline

Start

2014-04

Primary completion

2019-02

Completion

2021-01

Publications

• Results Umemura Y, Orringer D, Junck L, Varela ML, West MEJ, Faisal SM, Comba A, Heth J, Sagher O, Leung D, Mammoser A, Hervey-Jumper S, Zamler D, Yadav VN, Dunn P, Al-Holou W, Hollon T, Kim MM, Wahl DR, Camelo-Piragua S, Lieberman AP, Venneti S, McKeever P, Lawrence T, Kurokawa R, Sagher K, Altshuler D, Zhao L, Muraszko K, Castro MG, Lowenstein PR. Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. Lancet Oncol. 2023 Sep;24(9):1042-1052. doi: 10.1016/S1470-2045(23)00347-9.
• Lowenstein PR, Castro MG. Evolutionary basis of a new gene- and immune-therapeutic approach for the treatment of malignant brain tumors: from mice to clinical trials for glioma patients. Clin Immunol. 2018 Apr;189:43-51. doi: 10.1016/j.clim.2017.07.006. Epub 2017 Jul 15.

Drugs

Indications