Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations

Delta-24-based oncolytic viruses are conditional replication adenoviruses developed to selectively infect and replicate in retinoblastoma 1 (Rb)-deficient cancer cells but not normal cell with intact Rb1 pathways. Over the years, there has been a significant evolution in the design of Delta-24 based on a better understanding of the underlying basis for infection, replication, and spread within cancer. One example is the development of Delta-24-RGD (DNX-2401), where the arginine-glycine-aspartate (RGD) domain enhances the infectivity of Delta-24 for cancer cells. DNX-2401 demonstrated objective biological and clinical responses during a phase I window of opportunity clinical trial for recurrent human glioblastoma. In long-term responders (> 3 years), there was evidence of immune infiltration (T cells and macrophages) into the tumor microenvironment with minimal toxicity. Although more in-depth analysis and phase III studies are pending, these results indicate that Delta-24-based adenovirus therapy may induce an antitumor response in glioblastoma, resulting in long-term antitumor immune response. In this review, the authors discuss the preclinical and clinical development of Delta-24 oncolytic adenoviral therapy for glioblastoma and describe structural improvements to Delta-24 that have enhanced its efficacy in vivo. They also highlight ongoing research that attempts to address the remaining obstacles limiting efficacy of Delta-24 adenovirus therapy for glioblastoma.

Automated summary

Delta-24-based oncolytic viruses have evolved over the years with structural improvements to enhance infectivity for cancer cells while minimizing toxicity to normal cells. Clinical trials have demonstrated potential antitumor responses with immune cell infiltration in the tumor microenvironment, suggesting a promising long-term antitumor immune response.ongoing research aims to address the remaining obstacles limiting the efficacy of Delta-24 adenovirus therapy for glioblastoma.