Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Patient's own immune cells may blunt viral therapy for brain cancer

26.11.2012
People with a type of brain tumor called glioblastoma live 12 months on average, so new forms of treatment for this malignancy are badly needed.

Viruses designed to kill cancer cells offer a safe way to treat these tumors, but the therapy doesn't work as well as expected.

This study found that a patient's immune system tries to eliminate the anticancer virus and blocking this immune activity gave the virus more time to kill cancer cells.

Doctors now use cancer-killing viruses to treat some patients with lethal, fast-growing brain tumors. Clinical trials show that these therapeutic viruses are safe but less effective than expected.

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) shows that the reason for this is in part due to the patient's own immune system, which quickly works to eliminate the anticancer virus.

The findings, published in the journal Nature Medicine, show that the body responds to the anticancer virus 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," says co-senior 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," says Caligiuri, who is also the John L. Marakas Nationwide Insurance Enterprise Foundation Chair in Cancer Research. This study of cancer-cell-killing, or oncolytic, viruses is an example of the value 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," says 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:

Replication of the therapeutic virus in tumor cells in an animal model rapidly attracted subsets of NK cells to the tumor site;

NK cells in tumors activated other immune cells (i.e., macrophages and microglia) that have both antiviral and anticancer properties;

Depletion of NK cells improves the survival of tumor-bearing mice treated with the therapeutic virus;

NK cells that destroy 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," Caligiuri says.

Funding from the U.S. National Institutes of Health/NINDS (grant NS061811), NCI (grants CA069246, CA68458, CA98472, and the National Center for Research Resources (grant RR025753), an American Medical Association Foundation Seed Grant, the Dardinger Neuro-oncology Laboratory and Pelotonia supported this research.

Other researchers involved in this study were Christopher A. Alvarez-Breckenridge, Jianhua Yu, Richard Price1, Jeffrey Wojton, Jason Pradarelli, Hsiaoyin Mao, Min Wei, Yan Wang, Shun He, Jayson Hardcastle, Soledad A. Fernandez and Balveen Kaur of Ohio State; Sean E. Lawler, now at University of Leeds, U.K.; Eric Vivier of Université de la Méditerranée, Marseille, France; Ofer Mandelboim of Hebrew University-Hadassah Medical School, Jerusalem, Israel; Alessandro Moretta of Università degli Studi di Genova, Genova, Italy.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 228-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Getting electrons to move in a semiconductor

25.04.2018 | Physics and Astronomy

Reconstructing what makes us tick

25.04.2018 | Physics and Astronomy

Cheap 3-D printer can produce self-folding materials

25.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>