Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene

Noemi García-Romero1,2, Irina Palacín-Aliana3,4, Susana Esteban-Rubio5

  • 1Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

Cells
|June 11, 2020
PubMed

Insights

Glioblastoma (GBM) treatment resistance is linked to gene loss. Newcastle disease virus (NDV) shows potential for treating GBM, especially when type I interferon gene deletions are present.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis, often linked to cancer stem cells (CSCs) and therapy resistance.
  • Loss of the CDKN2A gene, near type I interferon (IFN) genes on chromosome 9p21, is common in GBM.
  • Newcastle disease virus (NDV), an avian paramyxovirus, possesses oncolytic and immunostimulatory properties, making it a candidate for GBM treatment.

Purpose of the Study:

  • To investigate the role of the CDKN2A-IFN I gene cluster in GBM.
  • To evaluate the efficacy of NDV as an oncolytic agent against GBM, particularly in relation to type I IFN gene status.
  • To explore strategies for overcoming NDV resistance in GBM.

Main Methods:

  • Analysis of the CDKN2A-IFN I gene cluster in 1018 glioma tumor samples.
  • Assessment of NDV oncolytic effects on six GBM CSCs ex vivo.
  • Evaluation of NDV efficacy in a mouse model of GBM.
  • Testing of NDV engineered to express influenza virus NS1 protein.

Main Results:

  • Over 50% of GBM patients exhibit deletions within the type I IFN gene cluster.
  • GBM susceptibility to NDV oncolysis is significantly influenced by the presence or absence of type I IFN genes.
  • Engineered NDV expressing influenza virus NS1 protein can overcome resistance in type I IFN-competent GBM cells.

Conclusions:

  • Type I IFN gene status is a critical factor determining GBM response to NDV therapy.
  • NDV holds promise as an oncolytic agent for GBM, especially in tumors with specific genetic alterations.
  • Genetically modified NDV vectors offer a potential strategy to enhance antitumor efficacy in GBM.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.0K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.7K