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

Neurosurg Focus. 2021 Feb;50(2):E6. doi: 10.3171/2020.11.FOCUS20853.


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.

Keywords: Delta-24; adenovirus; glioblastoma; oncolytic virus; retinoblastoma gene mutation.

Publication types

  • Review

MeSH terms

  • Adenoviridae / genetics
  • Cell Line, Tumor
  • Glioblastoma* / therapy
  • Humans
  • Neoplasm Recurrence, Local
  • Oncolytic Virotherapy*
  • Oncolytic Viruses* / genetics
  • Tumor Microenvironment