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Patient's own immune cells may blunt viral therapy for brain cancer
Date:11/25/2012

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.
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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