Journal
NEUROSURGICAL FOCUS
Volume 50, Issue 2, Pages -Publisher
AMER ASSOC NEUROLOGICAL SURGEONS
DOI: 10.3171/2020.11.FOCUS20853
Keywords
adenovirus; Delta-24; oncolytic virus; retinoblastoma gene mutation; glioblastoma
Categories
Funding
- National Cancer Institute [1R01CA214749, 1R01CA247970, 2P50CA127001]
- University of Texas MD Anderson Moon Shots Program
- Broach Foundation for Brain Cancer Research
- Priscilla and Jason Hiley Fund
- Baumann Family/CureFest Fund
- Elias Family Fund
- Jim and Pam Harris Fund
- Gene Pennebaker Brain Cancer Fund
- Schneider Memorial Fund
- Sweet Family Cancer Research Fund
- Dr. Marnie Rose Foundation
- Gold Family Memorial Fund
- Sorenson Foundation
Ask authors/readers for more resources
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.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available