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Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations
- Source :
- Neurosurgical focus. 50(2)
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 030218 nuclear medicine & medical imaging
Adenoviridae
03 medical and health sciences
0302 clinical medicine
Immune system
In vivo
Cell Line, Tumor
Tumor Microenvironment
Medicine
Humans
Oncolytic Virotherapy
Tumor microenvironment
business.industry
Retinoblastoma
Cancer
General Medicine
medicine.disease
Oncolytic virus
Clinical trial
Oncolytic Viruses
Cancer cell
Cancer research
Surgery
Neurology (clinical)
Neoplasm Recurrence, Local
business
Glioblastoma
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10920684
- Volume :
- 50
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Neurosurgical focus
- Accession number :
- edsair.doi.dedup.....15980647282cb136d69536f12d5a8db5