Abstract
Oncolytic adenoviruses are emerging as serious candidates for cancer treatment. Delta-24-RGD (DNX-2401) is an oncolytic adenovirus designed to infect and replicate in tumor cells. DNX-2401 has been evaluated in adult patients with gliomas showing a safe profile and antitumor effect. These results encouraged us to translate this strategy to pediatric gliomas. The aim of this work was to evaluate the safety and the antitumor effect of DNX-2401 alone or combined with radiotherapy in High Grade Gliomas (pHGGs) and Diffuse Intrinsic Pontine Gliomas (DIPGs). DNX-2401 showed a potent antitumor effect in pHGG (N=5) and DIPGs (N=6) cell lines (IC50 ranging from 1 to 50 MOIs) that was mediated by an effective viral replication. Addition of radiotherapy improved the antitumor effect of DNX-2401, due to synergistic effect (CI<1). Intratumoral delivery of DNX-2401 in nude mice bearing orthotopic pHGG and DIPG tumors did not showed any toxicity and increased significantly the survival of mice, due to an effective antiglioma effect These preclinical results allowed us to propose a phase 1 clinical trial for naïve DIPGs to evaluate the safety and feasibility of injecting this virus into the pons. The patients are subjected to a tumor biopsy and intratumoral infusion of DNX-2401. Up to date two patients have been treated with the 1x1010vp and the procedure were well tolerated. We believe that the information acquired through this study could serve to develop or improve new therapies in the battle against DIPG and constitute a paradigm change in the treatment of this devastating tumor.