Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Brain Cancer Patient’s Own Immune Cells May Suppress Viral Therapy

By BiotechDaily International staff writers
Posted on 03 Dec 2012
Clinicians are now employing cancer-killing viruses to treat some patients with deadly, fast-growing brain tumors. Clinical trials have demonstrated that these therapeutic viruses are safe but less effective than once thought.

A new study led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James; Columbus, USA) revealed that the reason for this is partly caused by the patient’s own immune system, which quickly works to eliminate the anticancer virus.

The findings, published November 25, 2012, in the journal Nature Medicine, demonstrate that the body responds to the anticancer virus the same as it does to an infection. Within hours, specialized immune cells called natural killer (NK) cells move in to eliminate the therapeutic virus in the brain.

The researchers discovered that the NK cells attack the viruses when they express specific molecules on their surface called NKp30 and NKp46. “These receptor molecules enable the NK cells to recognize and destroy the anticancer viruses before the viruses can destroy the tumor,” stated cosenior author Dr. Michael A. Caligiuri, director of Ohio State’s Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute, and a senior author of the study. “When we blocked those receptors, the virus has more time to work, and mice with these brain tumors live longer. The next step is to block these molecules on NK cells in glioblastoma patients and see if we can improve their outcome,” said Dr. Caligiuri.

This study of cancer-cell-killing (oncolytic) viruses exemplifies the benefits of translational research, in which a problem observed during clinical trials is studied in the laboratory to devise a solution. “In this case, clinical trials of oncolytic viruses proved safe for use in the brain, but we noticed substantial numbers of immune cells in brain tumors after treatment,” remarked senior author and neurosurgeon Dr. E. Antonio Chiocca, who was professor and chair of neurological surgery while at Ohio State University. “To understand this process, we went back to the laboratory and showed that NK cells rapidly infiltrate tumors in mice that have been treated with the therapeutic virus. These NK cells also signal other inflammatory cells to come in and destroy the cancer-killing virus in the tumor.”

The study used an oncolytic herpes simplex virus, human glioblastoma tumor tissue and mouse models, one of which hosted both human glioblastoma cells and human NK cells. Key technical findings include: NK cells in tumors triggered other immune cells (i.e., microglia and macrophages) that have both antiviral and anticancer characteristics; replication of the therapeutic virus in tumor cells in an animal model quickly drew subsets of NK cells to the tumor site; depletion of NK cells improves the survival of tumor-bearing mice treated with the therapeutic virus; NK cells that kill virus-infected tumor cells express the NKp30 and NKp46 receptors molecules that recognize the virus.

“Once we identify the molecules on glioblastoma cells that these NK cell receptors bind with, we might be able to use them to identify patients who will be sensitive to this therapy,” Dr. Caligiuri concluded.

Related Links:

Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute




Channels

Genomics/Proteomics

view channel
Image: The photo shows a mouse pancreatic islet as seen by light microscopy. Beta cells can be recognized by the green insulin staining. Glucagon is labeled in red and the nuclei in blue (Photo courtesy of Wikimedia Commons).

Regenerative Potential Is a Trait of Mature Tissues, Not an Innate Feature of Newly Born Cells

Diabetes researchers have found that the ability of insulin-producing beta cells to replicate and respond to elevated glucose concentrations is absent in very young animals and does not appear until after weaning.... Read more

Drug Discovery

view channel
Image: Wafers like the one shown here are used to create “organ-on-a-chip” devices to model human tissue (Photo courtesy of Dr. Anurag Mathur, University of California, Berkeley).

Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Human heart cells growing in an easily monitored silicon chip culture system may one day replace animal-based model systems for drug development and safety screening. Drug discovery and development... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.